Cancer drug and uses

ABSTRACT

A pharmaceutical composition comprising a cancer therapeutic that is capable of inhibiting and/or reducing the ability of a cancer cell to take up and utilize glucose or other energy source, a lipid or other building block of a cell membrane or organelle, and/or cholesterol. The pharmaceutical composition can comprise one or more cancer therapeutics that can be administered individually or in combination to an individual.

This application is a continuation that claims priority pursuant to 35U.S.C. 120 to U.S. Non-Provisional application Ser. No. 14/155,320,filed Jan. 14, 2014, an application that claims priority pursuant to 35U.S.C. 119(e) to U.S. Provisional Patent Application 61/752,360, filedJan. 14, 2013, U.S. Provisional Patent Application 61/782,585, filedMar. 14, 2013, and U.S. Provisional Patent Application 61/872,822, filedSep. 2, 2013, each of which is hereby incorporated by reference in itsentirety.

BACKGROUND

The majority of cancer treatments are selected to inhibit or reduce acancer cells ability to survive and/or their ability to divide to formmore cancer cells. While currently there are many cancer treatments thatare prescribed to help an individual suffering from a cancer that haveone or both of these abilities, it is worth noting that these samecancer treatments have several shortcomings. Among these are that anindividual administered the treatment can suffer from a serious sideeffect. In addition, many treatments are cancer specific and only workon one type of cancer. Finally, their use is generally very costly andbeyond the reach of a large number of individuals suffering from acancer. What is needed is a treatment that has the ability to inhibit orreduce a cancer cells ability to survive and/or divide while at the sametime the treatment: (1) is tolerated by an individual; (2) works againstmany different cancers; and, (3) is affordable so that all individualssuffering from a cancer can be administered the treatment.

Currently, there are whole classes of therapeutics that are administeredto individuals who suffer from a genetic, metabolic or other disease orfrom a disease caused by a bacteria, virus or parasite (a “diseasetreating therapeutic”) that treat the disease by inhibiting or reducingthe ability of a cell to survive and/or divide. In particular, thesedisease therapeutics act by: (1) inhibiting or reducing the amount oflipids, other fats and/or cholesterol taken up by cells; and/or (2)inhibiting or reducing the ability of a cell to take up or utilizeglucose or another energy source. While these disease treatingtherapeutics act in a manner that can treat a cancer, currently they arenot prescribed to patients suffering from cancer.

Thus, it would be advantageous to use a disease treating therapeutic totreat cancer (hereinafter a “cancer therapeutic”). Such a cancertherapeutic can be administered to an individual either solely or incombination with one or more of additional cancer therapeutics to treata cancer. Moreover, as these cancer therapeutics affect a cancer cellsmetabolism and ability to divide, they can be used against multipledifferent cancer types, and in some instances, all cancers.

Most cancer therapeutics are provided to a patient suffering from acancer using a formulation that enables the therapeutic to dissolve inan aqueous solution that will mix with the patients plasma followingtransfusion. These formulations are more concerned with solubility andare not generally designed to enhance the effectiveness of the cancertherapeutic. One means of increasing the effectiveness of therapeuticsthat has been successful in the past is the use of lipid formulations.Lipid formulations have been shown to increase the effectiveness ofcertain classes of drugs, such as NSAIDs, while reducing some of theiradverse side effects.

Among the classes of cancer therapeutics that would benefit from a lipidformulation are Artemisinin and its derivatives. Artemisinin is purifiedfrom the leaves of Artemisia annua (annual wormwood). The drug is namedQinghaosu in Chinese. Artemisia annua is a common herb and has beenfound in many parts of the world. Artemisinin, and its derivatives are agroup of drugs that are known to have a rapid action in patients for thetreatment of Plasmodium falciparum malaria. Treatments containing anartemisinin derivative (artemisinin-combination therapies, ACTs) are nowstandard treatment worldwide for P. falciparum malaria.

Use of the drug by itself as a monotherapy is explicitly discouraged bythe World Health Organization, as there have been signs that malarialparasites are developing resistance to the drug. Therapies that combineartemisinin with some other antimalarial drug are the preferredtreatment for malaria and are both effective and well tolerated inpatients. The drug is also increasingly being used in Plasmodium vivaxmalaria, as well as being a topic of research in cancer treatment(http://en.wikipedia.org).

Because artemisinin itself has physical properties such as poorbioavailability that limit its effectiveness, semisynthetic derivativesof artemisinin have been developed. These include: Artesunate,Artemether, Dihydroartemisinin, Artelinic acid, Artenimol and Artemotil.There are also simplified analogs in preclinical research, including,arterolane.

Artemisinin and its derivatives have been shown in some studies to havesome anticancer and antitumor activity. For instance, Arthemether hasshown a strong inhibitory effects on brain glioma growth andangiogenesis in rats. It has also shown a dose- and time-dependentcytotoxicity that induced apoptosis and G2 cell cycle arrest in ovariancancer cell lines, human leukemia HL60 cells, and human pancreaticcancer BxPC-3 and AsPC-1 cells. Dihydroartemisinin and otherartemisinin-based endoperoxide compounds have been found to target humanmetastatic melanoma cells with induction of NOXA-dependent mitochondrialapoptosis that occurs downstream of iron-dependent generation ofcytotoxic oxidative stress.

Other cancer therapeutics include drugs used as part of a chemotherapyregimen, including, alkylating agents, antimetabolites, anthracyclines,plant alkaloids, topoisomerase inhibitors, and other antitumour agents.Other cancer therapeutics include monoclonal antibodies and the newtyrosine kinase inhibitors, which directly target a molecularabnormality in certain types of cancer. Each of these other cancertherapeutics could benefit from a formulation that results in amaintenance or reduction of the number of cancer cells a patient has orthe size of one or more tumors present in a patient.

While these cancer therapeutics function for their intended purpose,their effectiveness can be improved through a formulation that enhancestheir ability to act on their target cells. One means of doing this isto formulate cancer therapeutics in a lipid formulation.

SUMMARY

In an aspect of the present invention, a pharmaceutical compositioncomprising a therapeutic is used to treat a cancer (a “cancertherapeutic”). In an embodiment, a cancer therapeutic or derivativethereof, affects cellular metabolism. In an embodiment, a cancertherapeutic reduces the amount of circulating glucose in an individual.In another embodiment, a cancer therapeutic reduces the amount ofcirculating lipids, other fats and/or cholesterol.

In an embodiment, a cancer therapeutic can enter a macrophage resultingin the macrophage increasing the level of CD36 and LDL receptors,resulting in a reduction in circulating LDLs. In another embodiment, acancer therapeutic increases the Glut-4 receptor on muscle cells, whichresults in a reduction in circulating glucose. In a further embodiment,a cancer therapeutic is one that removes and accepts electrons frommolecules that results in the interference of the glycolytic process ina cell.

In an embodiment, a cancer therapeutic results in a cancer cell notbeing able to uptake sufficient quantities of glucose or another energysource resulting in the cell entering apoptosis and eventually dying. Ina further embodiment, a cancer therapeutic results in a cell not beingable to uptake sufficient quantities of a lipid, other fat and/orcholesterol, preventing the cancer cell from dividing and forming aprogeny cancer cell.

In an aspect, the present invention is a pharmaceutical compositioncomprising a cancer therapeutic and a pharmaceutically acceptable lipidformulation. In a further aspect, the present invention is a cancertherapeutic is Artemisnin or a derivative thereof, including, withoutlimitation, Artesunate, Artemether, Dihydroartemisinin, Artelinic acid,Artenimol and/or Artemotil. In an aspect the present invention includesa pharmaceutically acceptable solvent, a pharmaceutically acceptablestabilizing agent, pharmaceutically acceptable carrier and/or apharmaceutically acceptable component.

In an aspect of the present invention, the cancer therapeutic is analkylating agent, including, without limitation Cisplatin, carboplatin,mechlorethamine, cyclophosphamide, chlorambucil, ifosfamide and/oroxaliplatin. In a further aspect of the present invention, the cancertherapeutic is an anti-metabolite, including, without limitation,azathioprine and/or mercaptopurine and wherein, without limitation, theanti-metabolite is a synthetic, semisynthetic or derivative of ananti-metabolite. In an aspect of the present invention, the cancertherapeutic is a terpenoid, including, without limitation, a vincaalkaloid and/or a taxane, and further wherein, without limitation, thevinca alkaloid is Vincristine, Vinblastine, Vinorelbine and/or Vindesineand further, without limitation, the taxane is Taxol, Pacllitaxel and/orDocetaxel and further wherein, without limitation, the taxane is asynthetic, semisynthetic or derivative of a taxane. In an aspect, thepresent invention the cancer therapeutic is a topoisomerase, and furtherwherein, without limitation, the topoisomerase is a type I topoisomeraseand/or a type 2 topoisomerase. In an aspect, the present invention, thetype 1 topoisomerase is camptothecins, and further wherein, thecamptothecins is irinotecan and/or topotecan. In an aspect, the type IItopoisomerase is amsacrine, etoposide, etoposide phosphate and/orteniposide, and further, wherein, without limitation, the topoisomeraseis a synthetic, semisynthetic and/or derivative. In a further aspect ofthe present invention, the derivative is epipodophyllotoxins. In anaspect of the present invention, the cancer therapeutic is a cytotoxicantibiotic, and further wherein, without limitation, the cytotoxicantibiotic is actinomycin, anthracyclines, doxorubicin, daunorubicin,valrubicin, idarubicin, epirubicin, bleomycin, plicamycin and/ormitomycin. In an aspect of the present invention, the cancer therapeuticis a hormone, and further wherein, without limitation, the hormone is alutenizing hormone releasing hormone agonist and further wherein,without limitation, the hormone is leuprolidine, goserelin, triptorelin,histrelin, bicalutamide, flutamide and/or nilutamide. In an aspect ofthe present invention, the cancer therapeutic is an antibody, andfurther wherein, without limitation, the antibody is Abciximab,Adalimumab, Alemtuzumab, Atlizumab, Basiliximab, Belimumab, Bevacizumab,Bretuximab vedotin, Canakinumab, Cetuximab, Ceertolizumab pegol,Daclizumab, Denosumab, Eculizumab, Efalizumab, Gemtuzumab, Golimumab,Golimumab, Ibritumomab tiuxetan, Infliximab, Ipilimumab, Muromonab-CD3,Natalizumab, Ofatumumab, Omalizumab, Palivizumab, Panitumuab,Ranibizumab, Rituximab, Tocilizumab, Tositumomab and/or Trastuzumab. Inan aspect of the present invention, the artemesinin derivative is abutyrate ester of dihydroartemesinin.

In an aspect of the present invention, the cancer therapeutic is capableof reducing the number of cancer cells or tumor size in an individualsuffering from a cancer by, e.g., at least 10%, at least 15%, at least20%, at least 25%, at least 30%, at least 35%, at least 40%, at least45%, at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90% or at least95% as compared to a patient not receiving the same treatment. In otheraspects of this embodiment, a therapeutic compound capable of reducingthe number of cancer cells or tumor size in an individual suffering froma cancer by, e.g., about 10% to about 100%, about 20% to about 100%,about 30% to about 100%, about 40% to about 100%, about 50% to about100%, about 60% to about 100%, about 70% to about 100%, about 80% toabout 100%, about 10% to about 90%, about 20% to about 90%, about 30% toabout 90%, about 40% to about 90%, about 50% to about 90%, about 60% toabout 90%, about 70% to about 90%, about 10% to about 80%, about 20% toabout 80%, about 30% to about 80%, about 40% to about 80%, about 50% toabout 80%, or about 60% to about 80%, about 10% to about 70%, about 20%to about 70%, about 30% to about 70%, about 40% to about 70%, or about50% to about 70% as compared to a patient not receiving the sametreatment.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the results for samples assessed 72 hours after wellscontaining MCF-7 cells (or no cells in a control) were administered asingle dose of Artesunate and/or Sodium Butyrate.

FIG. 2 shows the results for samples assessed 72 hours after wellscontaining MCF-7 cells (or no cells in a control) were administeredmultiple doses (at 24 and 48 hours) of Artesunate and/or SodiumButyrate.

FIG. 3 shows the results for samples assessed 72 hours after wellscontaining MCF-7 cells (or no cells in a control) were administered asingle dose of Artesunate and/or Resveratrol, Daidzein or Equol or nodrug (far right panel).

FIG. 4 shows the results for samples assessed 72 hours after wellscontaining MCF-7 cells (or no cells in a control) were administeredmultiple doses of Artesunate and/or Resveratrol, Daidzein or Equol or nodrug (far right panel).

DESCRIPTION

Aspects of the present specification disclose, in part, a therapeuticcompound. A therapeutic compound, includes, but is not limited to, acancer therapeutic. A therapeutic compound is a compound that providespharmacological activity or other direct effect in the diagnosis, cure,mitigation, treatment, or prevention of cancer, or to affect thestructure or any function of the body of man or animals. A therapeuticcompound disclosed herein may be used in the form of a pharmaceuticallyacceptable salt, solvate, or solvate of a salt, e.g. the hydrochloride.Additionally, therapeutic compound disclosed herein may be provided asracemates, or as individual enantiomers, including the R- orS-enantiomer. Thus, the therapeutic compound disclosed herein maycomprise a R-enantiomer only, a S-enantiomer only, or a combination ofboth a R-enantiomer and a S-enantiomer of a therapeutic compound. Atherapeutic compound disclosed herein may have anti-cancer activity.

In an embodiment, a cancer therapeutic is an alkylating agent.Alkylating agents are so named because of their ability to alkylate manynucleophilic functional groups under conditions present in cells,including, but not limited to cancer cells. In a further embodiment, analkylating agent includes, but is not limited to, Cisplatin,carboplatin, mechlorethamine, cyclophosphamide, chlorambucil, ifosfamideand/or oxaliplatin. In an embodiment, alkylating agents can function byimpairing cell function by forming covalent bonds with the amino,carboxyl, sulfhydryl, and phosphate groups in biologically importantmolecules or they can work by modifying a cell's DNA. In a furtherembodiment an alkylating agent is a synthetic, semisynthetic orderivative.

In an embodiment, a cancer therapeutic is an anti-metabolite.Anti-metabolites masquerade as purines or pyrimidines, thebuilding-blocks of DNA and in general, prevent these substances frombecoming incorporated in to DNA during the “S” phase (of the cellcycle), stopping normal development and division. Anti-metabolites canalso affect RNA synthesis. In an embodiment, an antimetabolite includes,but is not limited to azathioprine and/or mercaptopurine. In a furtherembodiment an anti-metabolite is a synthetic, semisynthetic orderivative.

In an embodiment, a cancer therapeutic is a plant alkaloid and/orterpenoid. These alkaloids are derived from plants and block celldivision by, in general, preventing microtubule function. In anembodiment, a plant alkaloid and/or terpenoid is a vinca alkaloid, apodophyllotoxin and/or a taxane. Vinca alkaloids, in general, bind tospecific sites on tubulin, inhibiting the assembly of tubulin intomicrotubules, generally during the M phase of the cell cycle. In anembodiment, a vinca alkaloid is derived, without limitation, from theMadagascar periwinkle, Catharanthus roseus (formerly known as Vincarosea). In an embodiment, a vinca alkaloid includes, without limitation,Vincristine, Vinblastine, Vinorelbine and/or Vindesine. In anembodiment, a taxane includes, but is not limited, to Taxol, Paclitaxeland/or Docetaxel. In a further embodiment a plant alkaloid or terpernoidis a synthetic, semisynthetic or derivative. In a further embodiment, apodophyllotoxin is, without limitation, an etoposide and/or teniposide.In an embodiment, a taxane is, without limitation, docetaxel and/orortataxel.

In an embodiment, a cancer therapeutic is a topoisomerase.Topoisomerases are essential enzymes that maintain the topology of DNA.Inhibition of type I or type II topoisomerases interferes with bothtranscription and replication of DNA by upsetting proper DNAsupercoiling. In a further embodiment, a topoisomerase is, withoutlimitation, a type I topoisomerase inhibitor or a type II topoisomeraseinhibitor. In an embodiment a type I topoisomerase inhibitor is, withoutlimitation, a camptothecin. In another embodiment, a camptothecin is,without limitation, exatecan, irinotecan, lurtotecan, topotecan, BNP1350, CKD 602, DB 67 (AR67) and/or ST 1481. In an embodiment, a type IItopoisomerase inhibitor is, without limitation, epipodophyllotoxin. In afurther embodiment an epipodophyllotoxin is, without limitation, anamsacrine, etoposid, etoposide phosphate and/or teniposide. In a furtherembodiment a topoisomerase is a synthetic, semisynthetic or derivative,including those found in nature such as, without limitation,epipodophyllotoxins, substances naturally occurring in the root ofAmerican Mayapple (Podophyllum peltatum).

In an embodiment, a cancer therapeutic is a stilbenoid. In a furtherembodiment, a stilbenoid includes, but is not limited to, Resveratrol,Piceatannol, Pinosylvin, Pterostilbene, Alpha-Viniferin, Ampelopsin A,Ampelopsin E, Diptoindonesin C, Diptoindonesin F, Epsilon-Vinferin,Flexuosol A, Gnetin H, Hemsleyanol D, Hopeaphenol, Trans-DiptoindonesinB, Astringin, Piceid and Diptoindonesin A. In a further embodiment astilbenoid is a synthetic, semisynthetic or derivative.

In an embodiment, a cancer therapeutic is an isoflavone. In a furtherembodiment, a isoflavone includes, but is not limited to, Daidzein andGenistein. In a further embodiment a isoflavone is a synthetic,semisynthetic or derivative.

In an embodiment, a cancer therapeutic is an isoflavandiol. In a furtherembodiment, an isoflavandiol includes, but is not limited to, Equol. Inan embodiment, Equol is one of two enantiomeric forms, either (5)-Equoland (R)-Equol. In a further embodiment a isoflavandiol is a synthetic,semisynthetic or derivative.

In an embodiment, a cancer therapeutic is a cytotoxic antibiotic. In anembodiment, a cytotoxic antibiotic is, without limitation, anactinomycin, an anthracenedione, an anthracycline, thalidomide,dichloroacetic acid, nicotinic acid, 2-deoxyglucose and/or chlofazimine.In an embodiment, an actinomycin is, without limitation, actinomycin D,bacitracin, colistin (polymyxin E) and/or polymyxin B. In anotherembodiment, an antracenedione is, without limitation, mitoxantroneand/or pixantrone. In a further embodiment, an anthracycline is, withoutlimitation, bleomycin, doxorubicin (Adriamycin), daunorubicin(daunomycin), epirubicin, idarubicin, mitomycin, plicamycin and/orvalrubicin. In a further embodiment a cytotoxic antibiotic is asynthetic, semisynthetic or derivative.

In an embodiment, a cancer therapeutic is a hormone. In an embodiment ahormone includes, but is not limited to, lutenizing hormone releasinghormone agonists. In an embodiment, a hormone includes, withoutlimitation, leuprolidine, goserelin, triptorelin, histrelin,bicalutamide, flutamide and nilutamide.

In an embodiment, a cancer therapeutic is an antibody. In an embodiment,an anticancer antibody includes, but is not limited to, Abciximab,Adalimumab, Alemtuzumab, Atlizumab, Basiliximab, Belimumab, Bevacizumab,Bretuximab vedotin, Canakinumab, Cetuximab, Ceertolizumab pegol,Daclizumab, Denosumab, Eculizumab, Efalizumab, Gemtuzumab, Golimumab,Golimumab, Ibritumomab tiuxetan, Infliximab, Ipilimumab, Muromonab-CD3,Natalizumab, Ofatumumab, Omalizumab, Palivizumab, Panitumuab,Ranibizumab, Rituximab, Tocilizumab, Tositumomab, Trastuzumab and/or anyother known or developed antibody that functions as a cancertherapeutic.

In an embodiment, a cancer therapeutic is, without limitation, a statin.In a further embodiment, without limitation, a statin is, withoutlimitation, atorvastatin, fluvastin, lovastatin, pitavastatin,pravastatin, rosuvastatin and/or simvastatin.

In an embodiment, a cancer therapeutic is, without limitation, atherapeutic for the treatment of diabetes. In an embodiment, atherapeutic for the treatment of diabetes is, without limitation, abiguanide, a thiazolidinedione, a secretagogue, an alpha-glucosidaseinhibitor and/or a peptide analog. In an embodiment, a biguanide is,without limitation, metformin, phenformin and/or buformin. In anotherembodiment, a thiazolidinedione is, without limitation, rosiglitazone,pioglitazone and/or troglitazone. In an embodiment, a secretagogue is,without limitation, a sulfonylurea, a nonsulfonylurea and/or ameglitinide. In a further embodiment, a sulfonylurea is, withoutlimitation, tolbutamide, acetohexamide, tolazamide, chlorpropamide,glipzide, glyburide, glimepiride, gliclazide, glycopyramide and/orgliquidone. In an embodiment, a meglitinide is, without limitation,repaglinide and/or nateglinide. In an embodiment, an alpha-glucosidaseinhibitor is, without limitation, miglitol, acarbose and/or voglibose.In an embodiment, a peptide analog is, without limitation, an injectableincretin mimetic, an injectable glucagon-like peptide analog and/oragonist, a gastric inhibitory peptide analog, a dipeptidyl peptidase-4inhibitor and/or an injectable Amylin analogue. In a further embodiment,an injectable glucagon-like peptide analog and/or agonist is, withoutlimitation, exenatide, liraglutide and/or taspoglutide. In a furtherembodiment, a dipeptidyl peptidase-4 inhibitor is, without limitation,vildagliptin, sitagliptin, saxagliptin, linagliptin, allogliptin and/orseptagliptin. In another embodiment, an injectable Amylin analogue is,without limitation, pramlintide. In an embodiment, a therapeutic for thetreatment of diabetes is cinnamon and/or thiamine.

In an embodiment, a cancer therapeutic is, without limitation, aPeroxisome proliferator-activated receptor gamma (PPAR-y or PPARG)agonist. In a further embodiment, a PPAR-y is, without limitation,rosiglitazone, troglitazone, pioglitazone, netoglitazone, rivoglitazoneand/or ciglitazone.

In an embodiment, a cancer therapeutic is a PPAR-13 agonist. In anotherembodiment, a PPAR-13 agonist is, without limitation, endurobol and/orGW0742.

In an embodiment, a cancer therapeutic is a PPAR-a agonist.

In an embodiment, a cancer therapeutic is, without limitation anantibiotic. In another embodiment, an antibiotic is, without limitation,isoniazid, rifampicin, pyrazinamide and/or ethambutol.

In an embodiment, a cancer therapeutic is, without limitation, anantihelminthic. In a further embodiment, an antihelminthic is, withoutlimitation, abamectin, an aminoacetonitriles, a benzimadazole,diethylcaramazine, ivermectin, levamisole, niclosamide, anoctadepsipeptides, phosphoric acid (metrifonate), praziquantel, aspiroindoles, suramin and/or pyrantel pamoate. In a further embodiment,an aminoacetonitrile is, without limitation, monepantel. In anotherembodiment, a benzimidazole is, without limitation, albendazole,fenbendazole, a flubendazole, thiabendazole and triclabendazole. In anembodiment, a flubendazole is, without limitation, mebendazole. Inanother embodiment, an octadepsipeptide is, without limitation,emodepside. In a further embodiment, a spiroindole is, withoutlimitation, dequantel.

In an embodiment, a cancer therapeutic is, without limitation, a foodadditive and/or a vitamin. In a further embodiment, a food additiveand/or vitamin is, without limitation, tributerin, vitamin C, vitamin812, vitamin D, resveratrol and/or coenzymeQ12.

In an embodiment, a cancer therapeutic is, without limitation, a glucoseintake inhibitor. In another embodiment, a glucose intake inhibitor is,without limitation, a GLUT-1 receptor inhibitor.

In an embodiment a cancer therapeutic is, without limitation, a lipidintake inhibitor. In a further embodiment, a lipid intake inhibitor is,without limitation, an LDL receptor inhibitor, an SR-81 inhibitor, anSR-82 inhibitor and/or a SR-83/CD36 (thrombospondin) receptor inhibitor.

In an embodiment, a cancer therapeutic is a glycolysis inhibitor. Inanother embodiment, a glycolysis inhibitor is, without limitation, ahexokinase inhibitor, a phosphoglucose isomerase inhibitor, afructosebisphosphate inhibitor, a triosephosphate isomerase inhibitor, aglyceraldehyde phosphate dehydrogenase inhibitor, a phsphoglyceratekinase inhibitor, a phosphoglycerate mutase inhibitor, an enolaseinhibitor and/or a pyruvate kinase inhibitor.

In an embodiment, a cancer therapeutic is, without limitation, ananti-malarial therapeutic. In a further embodiment, an anti-malarialtherapeutic is, without limitation, amodiaquine, an artemisinin,atovaquone, chloroquine, clindamycin, doxycycline, halofantrine,mefloquine, primaquine, proguanil, pyrimethamine, a quinine and relatedagent, rufigallol, and/or a sulphonamide. In another embodiment, anartemisinin is, without limitation, arteether, artemether, artemisinin,artesunate and/or dihydroartemisinin. In another embodiment, a quinineand related agent is, without limitation, quinimax and/or quinidine. Inanother embodiment, a sulfonamide is, without limitation, sulfadoxineand/or sulfamethoxypyri dazine.

In an embodiment, a cancer therapeutic is Artemisinin. In a furtherembodiment, a cancer therapeutic is a derivative of Artemesinin.Derivatives of Artemesinin include, but are not limited to, Artesunate,Artemether, Dihydroartemisinin, Artelinic acid, arterolane, Artenimoland Artemotil.

In an embodiment, Artesunate is prepared from dihydroartemisinin (DHA)by reacting it with succinic acid anhydride in basic medium. Pyridine asbase/solvent, sodium bicarbonate in chloroform and catalyst DMAP(N,N-dimethylaminopyridine) and triethylamine in 1,2-dichloroethane havebeen used, with yields of up to 100%. A large scale process involvestreatment of DHA in dichloromethane with a mixture of pyridine, acatalytic amount of DMAP and succinic anhydride. The dichloromethanemixture is stirred for 6-9 h to get artesunate in quantitative yield.The product is further re-crystallized from dichloromethane.a-Artesunate is exclusively formed (m.p 135-137° C.).

In an embodiment, Artemether is a methyl ether derivative ofartemisinin, which is a peroxide lactone isolated from the Chineseantimalarial plant, Artemisia annua. It is also known asdihydroartemisinin methyl ether, but its correct chemical nomenclatureis (+)-(3-alpha,5a-beta,6-beta,8a-beta,9-alpha,12-beta,12aR)-decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin.It is a relatively lipophilic and unstable drug.

In an embodiment, Dihydroartemisinin is the active metabolite of allartemisinin compounds (artemisinin, artesunate, artemether, etc.) and isalso available as a drug in itself. It is a semi-synthetic derivative ofartemisinin and is widely used as an intermediate in the preparation ofother artemisinin-derived antimalarial drugs. Dihydroartemisinin is theactive metabolite of all artemisinin compounds (artemisinin, artesunate,artemether, etc.) and is also available as a drug in itself. It is asemi-synthetic derivative of artemisinin and is widely used as anintermediate in the preparation of other artemisinin-derivedantimalarial drugs.

In an embodiment, Artelinic acid (or its salt, artelinate) is asemi-synthetic derivative of the natural compound artemisinin. Artelinicacid has a lower rate of neurotoxicity than the related artemisinderivatives arteether and artemether.

In an embodiment, Artemotil (INN; also known as β-arteether), is asemi-synthetic derivative of artemisinin, a natural product of theChinese plant Artemisia annua.

In an embodiment, a cancer therapeutic is a butyrate ester ofdihydroartemesinin with a structure that can include, but is not limitedto the following:

In an embodiment, a cancer therapeutic is a dichloroacetate ester.

In an embodiment, a patient is administered one or more of an alkylatingagent, an anti-metabolite, a plant alkaloid, a terpenoid, atopoisomerase inhibitor, a cytotoxic antibiotics, a statin, ananti-diabetic drug, a PPAR-y, a PPAR-13, a PPAR-a, an antibiotic, anantihelminthic, an anti-malaria drug, a vitamin and/or a food additive.In an embodiment, a patient is administered one or more cancertherapeutics. In an embodiment, a patient is administered one, two,three, four, five, six, seven eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen ortwenty different cancer therapeutics.

In an embodiment, a cancer therapeutic and its derivatives havehalf-lives of the order of 1 hour, and therefore require at least dailydosing over several days. In a further embodiment, a cancer therapeutic,includes, but not limited to, artemisinin and its derivatives havehalf-lives of 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22hours, 23 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days,1 week, 2 weeks, 3 weeks, 4 weeks, one month, two months, three months,four months or more.

In an embodiment, the period of administration of a cancer therapeuticis for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9days, 10 days, 11 days, 12 days, 13 days, 14 days, 3 weeks, 4 weeks, 5weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks,4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months,11 months, 12 months, or more. In a further embodiment, a period ofduring which administration is stopped is for 1 day, 2 days, 3 days, 4days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days,13 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks,9 weeks, 10 weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6 months, 7months, 8 months, 9 months, 10 months, 11 months, 12 months, or more.

In an embodiment, a therapeutic compound is administered to anindividual for a period of time followed by a separate period of time.In another embodiment, a therapeutic compound is administered for afirst period and a second period following the first period, withadministration stopped during the second period, followed by a thirdperiod where administration of the therapeutic compound is started andthen a fourth period following the third period where administration isstopped. In an aspect of this embodiment, the period of administrationof a therapeutic compound followed by a period where administration isstopped is repeated for a determined or undetermined period of time. Ina further embodiment, a period of administration is for 1 day, 2 days, 3days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days,12 days, 13 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks,8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months,or more. In a further embodiment, a period of during whichadministration is stopped is for 1 day, 2 days, 3 days, 4 days, 5 days,6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8months, 9 months, 10 months, 11 months, 12 months, or more.

In an embodiment, a first therapeutic compound is administered to anindividual and at a later date, a second therapeutic compound isadministered to the same individual. In aspects of this embodiment, thefirst therapeutic compound is artemesinin or a derivative thereof andthe second therapeutic compound is a different derivative ofartemesinin. In an embodiment, the first therapeutic compound isartemesinin or a derivative thereof and the second therapeutic compoundis a cancer therapeutic that is not artemesinin or a derivative thereof.

In an embodiment, a first therapeutic compound is administered to anindividual at the same time as a second therapeutic compound isadministered to the individual. In aspects of this embodiment, the firsttherapeutic compound is a artemesinin or derivative thereof and thesecond therapeutic compound is a different derivative of artemesinin. Inan embodiment, the first therapeutic compound is artemesinin or aderivative thereof and the second therapeutic compound is a cancertherapeutic that is not artemesinin or a derivative thereof.

Aspects of the present specification disclose, in part, a pharmaceuticalcomposition. As used herein, the term “pharmaceutically acceptable”means any molecular entity or composition that does not produce anadverse, allergic or other untoward or unwanted reaction whenadministered to an individual. As used herein, the term“pharmaceutically acceptable composition” is synonymous with“pharmaceutical composition” and means a therapeutically effectiveconcentration of an active ingredient, such as, e.g., any of thetherapeutic compounds disclosed herein. A pharmaceutical compositiondisclosed herein is useful for medical and veterinary applications. Apharmaceutical composition may be administered to an individual alone,or in combination with other supplementary active ingredients, agents,drugs or hormones.

A pharmaceutical composition disclosed herein may optionally include apharmaceutically-acceptable carrier that facilitates processing of anactive ingredient into pharmaceutically-acceptable compositions. As usedherein, the term “pharmacologically-acceptable carrier” is synonymouswith “pharmacological carrier” and means any carrier that hassubstantially no long term or permanent detrimental effect whenadministered and encompasses terms such as “pharmacologically acceptablevehicle, stabilizer, diluent, additive, auxiliary or excipient.” Such acarrier generally is mixed with an active compound or permitted todilute or enclose the active compound and can be a solid, semi-solid, orliquid agent. It is understood that the active ingredients can besoluble or can be delivered as a suspension in the desired carrier ordiluent. Any of a variety of pharmaceutically acceptable carriers can beused including, without limitation, aqueous media such as, e.g., water,saline, glycine, hyaluronic acid and the like; solid carriers such as,e.g., mannitol, lactose, starch, magnesium stearate, sodium saccharin,talcum, cellulose, glucose, sucrose, magnesium carbonate, and the like;solvents; dispersion media; coatings; antibacterial and antifungalagents; isotonic and absorption delaying agents; or any other inactiveingredient. Selection of a pharmacologically acceptable carrier candepend on the mode of administration. Except insofar as anypharmacologically acceptable carrier is incompatible with the activeingredient, its use in pharmaceutically acceptable compositions iscontemplated. Non-limiting examples of specific uses of suchpharmaceutical carriers can be found in Pharmaceutical Dosage Forms andDrug Delivery Systems (Howard C. Ansel et al., eds., Lippincott Williams& Wilkins Publishers, 7th ed. 1999); REMINGTON: THE SCIENCE AND PRACTICEOF PHARMACY (Alfonso R. Gennaro ed., Lippincott, Williams & Wilkins,20th ed. 2000); Goodman & Gilman's The Pharmacological Basis ofTherapeutics (Joel G. Hardman et al., eds., McGraw-Hill Professional,10th ed. 2001); and Handbook of Pharmaceutical Excipients (Raymond C.Rowe et al., APhA Publications, 4th edition 2003). These protocols areroutine procedures and any modifications are well within the scope ofone skilled in the art and from the teaching herein.

A pharmaceutical composition disclosed herein can optionally include,without limitation, other pharmaceutically acceptable components (orpharmaceutical components), including, without limitation, buffers,preservatives, tonicity adjusters, salts, antioxidants, osmolalityadjusting agents, physiological substances, pharmacological substances,bulking agents, emulsifying agents, wetting agents, sweetening orflavoring agents, and the like. Various buffers and means for adjustingpH can be used to prepare a pharmaceutical composition disclosed herein,provided that the resulting preparation is pharmaceutically acceptable.Such buffers include, without limitation, acetate buffers, citratebuffers, phosphate buffers, neutral buffered saline, phosphate bufferedsaline and borate buffers. It is understood that acids or bases can beused to adjust the pH of a composition as needed. Pharmaceuticallyacceptable antioxidants include, without limitation, sodiummetabisulfite, sodium thiosulfate, acetylcysteine, butylatedhydroxyanisole and butylated hydroxytoluene. Useful preservativesinclude, without limitation, benzalkonium chloride, chlorobutanol,thimerosal, phenylmercuric acetate, phenylmercuric nitrate, a stabilizedoxy chloro composition and chelants, such as, e.g., DTPA orDTPA-bisamide, calcium DTPA, and CaNaDTPA-bisamide. Tonicity adjustorsuseful in a pharmaceutical composition include, without limitation,salts such as, e.g., sodium chloride, potassium chloride, mannitol orglycerin and other pharmaceutically acceptable tonicity adjustor. Thepharmaceutical composition may be provided as a salt and can be formedwith many acids, including but not limited to, hydrochloric, sulfuric,acetic, lactic, tartaric, malic, succinic, etc. Salts tend to be moresoluble in aqueous or other protonic solvents than are the correspondingfree base forms. It is understood that these and other substances knownin the art of pharmacology can be included in a pharmaceuticalcomposition.

In one embodiment, a pharmaceutical composition disclosed hereincomprises a cancer therapeutic that has anti-cancer cell activity and apharmaceutically-acceptable lipid formulation. In another embodiment, apharmaceutical composition disclosed herein comprises a cancertherapeutic that has anti-cancer cell activity, apharmaceutically-acceptable solvent, and a pharmaceutically-acceptablelipid formulation. In aspects of this embodiment, a pharmaceuticalcomposition disclosed herein may further comprise apharmaceutically-acceptable stabilizing agent. In other aspects of thisembodiment, a pharmaceutical composition disclosed herein may furthercomprise a pharmaceutically-acceptable carrier, apharmaceutically-acceptable component, or bothpharmaceutically-acceptable carrier and pharmaceutically-acceptablecomponent.

In a further embodiment, a pharmaceutical composition comprises a cancertherapeutic that includes, without limitation, at least one of a statin,a treatment for diabetes, an antibiotic, a helminthic, a malarialtreatment a vitamin or a food additive. In an embodiment, apharmaceutical composition includes, without limitation, a statin, atreatment for diabetes, and a helminthic. In another embodiment, apharmaceutical composition includes, without limitation, a treatment fordiabetes, a statin, an antibiotic and a food additive. Furtherembodiments can include other combinations of two or more cancertherapeutics.

In an embodiment, an individual that is administered a cancertherapeutic suffers mild or no side-effects as a result of theadministered therapeutics.

In an embodiment, a cancer therapeutic is administered in conjunctionwith chemotherapy, radiation therapy, surgery, immunotherapy, including,without limitation, the derivation of stem cells and/or dendritic cellsblood transfusions, lavages, and/or other treatments, including, withoutlimitation, freezing a tumor. In a further embodiment, a cancertherapeutic is administered prior to or after the initiation andcompletion of chemotherapy, radiation therapy, immunotherapy, including,without limitation, the derivation of stem cells and/or dendritic cellsblood transfusions, lavages, and/or other treatments, including, withoutlimitation, freezing a tumor. In a further embodiment, a cancertherapeutic is administered, prior to, during and/or afteradministration of chemotherapy, radiation therapy, surgery,immunotherapy, including, without limitation, the derivation of stemcells and/or dendritic cells blood transfusions, lavages, and/or othertreatments, including, without limitation, freezing a tumor.

A therapeutic compound disclosed herein, or a pharmaceutical compositioncomprising such a therapeutic compound, may be formulated for eitherlocal or systemic delivery using topical, enteral or parenteral routesof administration. Additionally, a therapeutic compound disclosed hereinmay be formulated by itself in a pharmaceutical composition, or may beformulated together with one or more other therapeutic compoundsdisclosed herein in a single pharmaceutical composition.

A therapeutic compound disclosed herein, or a pharmaceutical compositioncomprising such a therapeutic compound, may be made into an inhaledformulation. Inhaled formulations suitable for enteral or parenteraladministration include, without limitation, aerosols, dry powders. Atherapeutic compound or composition disclosed herein intended for suchadministration may be prepared according to any method known to the artfor the manufacture of pharmaceutical compositions.

In such inhaled dosage forms, the therapeutic compound or apharmaceutical composition may be prepared for delivery as an aerosol ina liquid propellant for use in a pressurised (PDI) or other metered doseinhaler (MDI). Propellants suitable for use in a PDI or MDI include,without limitation, CFC-12, HFA-134a, HFA-227, HCFC-22(difluorochloromethane), HFA-152 (difluoroethane and isobutane). Atherapeutic compound may also be delivered using a nebulisers or otheraerosol delivery system. A therapeutic compound may be prepared fordelivery as a dry powder for use in a dry powder inhaler (DPI). A drypowder for use in the inhalers will usually have a mass medianaerodynamic diameter of less than 30 pm, preferably less than 20 pm andmore preferably less than 10 pm. Microparticles having aerodynamicdiameters in the range of about 5 pm to about 0.5 pm will generally bedeposited in the respiratory bronchioles, whereas smaller particles,having aerodynamic diameters in the range of about 2 pm to about 0.05pm, are likely to be deposited in the alveoli. A DPI may be a passivedelivery mechanism, which relies on the individual's inspiration tointroduce the particles into the lungs, or an active delivery mechanism,requiring a mechanism for delivering the powder to the individual. Ininhalatory formulations, a therapeutically effective amount of atherapeutic compound disclosed herein for an inhaled formulation may bebetween about 0.0001% (w/v) to about 60% (w/v), about 0.001% (w/v) toabout 40.0% (w/v), or about 0.01% (w/v) to about 20.0% (w/v). Ininhalatory formulations, a therapeutically effective amount of atherapeutic compound disclosed herein for an inhaled formulation mayalso be between about 0.0001% (w/w) to about 60% (w/w), about 0.001%(w/w) to about 40.0% (w/w), or about 0.01% (w/w) to about 20.0% (w/w).

A therapeutic compound disclosed herein, or a pharmaceutical compositioncomprising such a therapeutic compound, may be made into a solidformulation. Solid formulations suitable for enteral or parenteraladministration include, without limitation, capsules, tablets, pills,troches, lozenges, powders and granules suitable for inhalation or forreconstitution into sterile injectable solutions or dispersions. Atherapeutic compound or composition disclosed herein intended for suchadministration may be prepared according to any method known to the artfor the manufacture of pharmaceutical compositions. In such solid dosageforms, the therapeutic compound may be admixed with (a) at least oneinert customary excipient (or carrier), such as, e.g., sodium citrate ordicalcium phosphate or (b) fillers or extenders, as for example, starch,lactose, sucrose, glucose, mannitol, isomalt, and silicic acid, (c)binders, such as, e.g., carboxymethylcellulose, alignates, gelatin,polyvinylpyrrolidone, sucrose and acacia, (d) humectants, such as, e.g.,glycerol, (e) disintegrating agents, such as, e.g., agar-agar, calciumcarbonate, corn starch, potato starch, tapioca starch, alginic acid,certain complex silicates and sodium carbonate, (0 solution retarders,such as, e.g., paraffin, (g) absorption accelerators, such as, e.g.,quaternary ammonium compounds, (h) wetting agents, such as, e.g., cetylalcohol and glycerol monostearate, (i) adsorbents, such as, e.g., kaolinand bentonite, (j) lubricants, such as, e.g., talc, stearic acid,calcium stearate, magnesium stearate, solid polyethylene glycols, sodiumlauryl sulfate or mixtures thereof, and (k) buffering agents. Thetablets may be uncoated or they may be coated by known techniques todelay disintegration and absorption in the gastrointestinal tract andthereby provide a sustained action over a longer period. For example, atime delay material such as glyceryl monostearate or glyceryl distearatemay be employed. In solid formulations, a therapeutically effectiveamount of a therapeutic compound disclosed herein typically may bebetween about 0.0001% (w/w) to about 60% (w/w), about 0.001% (w/w) toabout 40.0% (w/w), or about 0.01% (w/w) to about 20.0% (w/w).

A therapeutic compound disclosed herein, or a pharmaceutical compositioncomprising such a therapeutic compound, may be made into a semi-solidformulation. Semi-solid formulations suitable for topical administrationinclude, without limitation, ointments, creams, salves, and gels. Atherapeutic compound or composition disclosed herein intended for suchadministration may be prepared according to any method known to the artfor the manufacture of pharmaceutical compositions. In semi-solidformulations, a therapeutically effective amount of a therapeuticcompound disclosed herein typically may be between about 0.0001% (w/v)to about 60% (w/v), about 0.001% (w/v) to about 40.0% (w/v), or about0.01% (w/v) to about 20.0% (w/v). In semi-solid formulations, atherapeutically effective amount of a therapeutic compound disclosedherein typically may also be between about 0.0001% (w/w) to about 60%(w/w), about 0.001% (w/w) to about 40.0% (w/w), or about 0.01% (w/w) toabout 20.0% (w/w).

A therapeutic compound disclosed herein, or a pharmaceutical compositioncomprising such a therapeutic compound, may be made into a liquidformulation. Liquid formulations suitable for enteral or parenteraladministration include, without limitation, solutions, syrups, elixirs,dispersions, emulsions, and suspensions, including, but not limited, tothose used for intravenous administration. A therapeutic compound orcomposition disclosed herein intended for such administration may beprepared according to any method known to the art for the manufacture ofpharmaceutical compositions. In such liquid dosage forms, a therapeuticcompound or composition disclosed herein may be admixed with (a)suitable aqueous and nonaqueous carriers, (b) diluents, (c) solvents,such as, e.g., water, ethanol, propylene glycol, polyethyleneglycol,glycerol, vegetable oils, such as, e.g., rapeseed oil and olive oil, andinjectable organic esters such as ethyl oleate; and/or fluidity agents,such as, e.g., surfactants or coating agents like lecithin. In the caseof dispersions and suspensions, fluidity can also be controlled bymaintaining a particular particle size. In liquid formulations, atherapeutically effective amount of a therapeutic compound disclosedherein typically may be between about 0.0001% (w/v) to about 60% (w/v),about 0.001% (w/v) to about 40.0% (w/v), or about 0.01% (w/v) to about20.0% (w/v).

Syrups and elixirs may be formulated with sweetening agents, for exampleglycerol, propylene glycol, sorbitol or sucrose. Such formulations mayalso contain a demulcent, a preservative, flavoring agents, and coloringagents.

Liquid suspensions may be formulated by suspending a therapeuticcompound disclosed herein in admixture with excipients suitable for themanufacture of aqueous suspensions. Such excipients are suspendingagents, for example sodium carboxymethylcellulose, methylcellulose,hydroxypropylmethylcellulose, sodium alginate, pectin, polyvinylpyrrolidone, polyvinyl alcohol, natural gum, agar, gum tragacanth andgum acacia; dispersing or wetting agents may be a naturally occurringphosphatide, for example lecithin, or condensation products of analkylene oxide with fatty acids, for example polyoxyethylene stearate,or condensation products of ethylene oxide with long-chain aliphaticalcohols, for example heptadecaethyleneoxycetanol, or condensationproducts of ethylene oxide with partial esters derived from fatty acids,for example polyoxyethylene sorbitan monooleate.

Oily suspensions may be formulated by suspending a therapeutic compounddisclosed herein in admixture with (a) vegetable oils, such as, e.g.,almond oil, arachis oil, avocado oil, canola oil, castor oil, coconutoil, corn oil, cottonseed oil, grape seed oil, hazelnut oil, hemp oil,linseed oil, olive oil, palm oil, peanut oil, rapeseed oil, rice branoil, safflower oil, sesame oil, soybean oil, soya oil, sunflower oil,walnut oil, wheat germ oil, or a combination thereof, (b) a saturatedfatty acid, an unsaturated fatty acid, or a combination thereof, suchas, e.g., palmitic acid, stearic acid, oleic acid, linoleic acid,linolenic acid, or a combination thereof, (c) mineral oil such as, e.g.,liquid paraffin, (d) surfactants or detergents. The oily suspensions maycontain a thickening agent, for example beeswax, hard paraffin or cetylalcohol. Sweetening agents, such as those set forth above, and flavoringagents may be added to provide a palatable oral preparation. Thesecompositions may be preserved by the addition of an antioxidant such asascorbic acid.

Dispersible powders and granules suitable for preparation of an aqueoussuspension by the addition of water provide the combined therapeuticcompounds in admixture with a dispersing or wetting agent, suspendingagent and one or more preservatives.

A therapeutic compound disclosed herein may be in the form ofoil-in-water emulsions. The oily phase may be a vegetable oil asdisclosed herein or a mineral oil as disclosed herein or mixturesthereof. Suitable emulsifying agents may be naturally occurring gums,such as, e.g., gum acacia or gum tragacanth, naturally occurringphosphatides, for example soya bean, lecithin, and esters or partialesters derived from fatty acids and hexitol anhydrides, for examplesorbitan monooleate and condensation products of the said partial esterswith ethylene oxide, for example polyoxyethylene sorbitan monooleate.

A therapeutic compound disclosed herein, or a composition comprisingsuch a therapeutic compound, may also be incorporated into a therapeuticcompound delivery platform in order to achieve a controlled releaseprofile over time. Such a therapeutic compound delivery platformcomprises a therapeutic compound disclosed herein dispersed within apolymer matrix, typically a biodegradable, bioerodible, and/orbioresorbable polymer matrix. As used herein, the term “polymer” refersto synthetic homo- or copolymers, naturally occurring homo- orcopolymers, as well as synthetic modifications or derivatives thereofhaving a linear, branched or star structure. Copolymers can be arrangedin any form, such as, e.g., random, block, segmented, tapered blocks,graft, or triblock. Polymers are generally condensation polymers.Polymers can be further modified to enhance their mechanical ordegradation properties by introducing cross-linking agents or changingthe hydrophobicity of the side residues. If crosslinked, polymers areusually less than 5% crosslinked, usually less than 1% crosslinked.

Suitable polymers include, without limitation, alginates, aliphaticpolyesters, polyalkylene oxalates, polyamides, polyamidoesters,polyanhydrides, polycarbonates, polyesters, polyethylene glycol,polyhydroxyaliphatic carboxylic acids, polyorthoesters, polyoxaesters,polypeptides, polyphosphazenes, polysaccharides, and polyurethanes. Thepolymer usually comprises at least about 10% (w/w), at least about 20%(w/w), at least about 30% (w/w), at least about 40% (w/w), at leastabout 50% (w/w), at least about 60% (w/w), at least about 70% (w/w), atleast about 80% (w/w), or at least about 90% (w/w) of the therapeuticcompound delivery platform. Examples of biodegradable, bioerodible,and/or bioresorbable polymers and methods useful to make a therapeuticcompound delivery platform are described in, e.g., Drost, et. al.,Controlled Release Formulation, U.S. Pat. No. 4,756,911; Smith, et. al.,Sustained Release Drug Delivery Devices, U.S. Pat. No. 5,378,475; Wongand Kochinke, Formulation for Controlled Release of Drugs by CombiningHyrophilic and Hydrophobic Agents, U.S. Pat. No. 7,048,946; Hughes, et.al., Compositions and Methods for Localized Therapy of the Eye, U.S.Patent Publication 2005/0181017; Hughes, Hypotensive Lipid-ContainingBiodegradable Intraocular Implants and Related Methods, U.S. PatentPublication 2005/0244464; Altman, et al., Silk Fibroin Hydrogels andUses Thereof, U.S. Patent Publication 2011/0008437; each of which isincorporated by reference in its entirety.

In aspects of this embodiment, a polymer composing the matrix is apolypeptide such as, e.g., silk fibroin, keratin, or collagen. In otheraspects of this embodiment, a polymer composing the matrix is apolysaccharide such as, e.g., cellulose, agarose, elastin, chitosan,chitin, or a glycosaminoglycan like chondroitin sulfate, dermatansulfate, keratan sulfate, or hyaluronic acid. In yet other aspects ofthis embodiment, a polymer composing the matrix is a polyester such as,e.g., D-lactic acid, L-lactic acid, racemic lactic acid, glycolic acid,caprolactone, and combinations thereof.

One of ordinary skill in the art appreciates that the selection of asuitable polymer for forming a suitable disclosed therapeutic compounddelivery platform depends on several factors. The more relevant factorsin the selection of the appropriate polymer(s), include, withoutlimitation, compatibility of polymer with a therapeutic compound,desired release kinetics of a therapeutic compound, desiredbiodegradation kinetics of platform at implantation site, desiredbioerodible kinetics of platform at implantation site, desiredbioresorbable kinetics of platform at implantation site, in vivomechanical performance of platform, processing temperatures,biocompatibility of platform, and patient tolerance. Other relevantfactors that, to some extent, dictate the in vitro and in vivo behaviorof the polymer include the chemical composition, spatial distribution ofthe constituents, the molecular weight of the polymer and the degree ofcrystallinity.

A therapeutic compound delivery platform includes both a sustainedrelease therapeutic compound delivery platform and an extended releasetherapeutic compound delivery platform. As used herein, the term“sustained release” refers to the release of a therapeutic compounddisclosed herein over a period of about seven days or more. As usedherein, the term “extended release” refers to the release of atherapeutic compound disclosed herein over a period of time of less thanabout seven days.

In aspects of this embodiment, a sustained release therapeutic compounddelivery platform releases a therapeutic compound disclosed herein withsubstantially zero order release kinetics over a period of, e.g., about7 days after administration, about 15 days after administration, about30 days after administration, about 45 days after administration, about60 days after administration, about 75 days after administration, orabout 90 days after administration. In other aspects of this embodiment,a sustained release therapeutic compound delivery platform releases atherapeutic compound disclosed herein with substantially zero orderrelease kinetics over a period of, e.g., at least 7 days afteradministration, at least 15 days after administration, at least 30 daysafter administration, at least 45 days after administration, at least 60days after administration, at least 75 days after administration, or atleast 90 days after administration.

In aspects of this embodiment, a sustained release therapeutic compounddelivery platform releases a therapeutic compound disclosed herein withsubstantially first order release kinetics over a period of, e.g., about7 days after administration, about 15 days after administration, about30 days after administration, about 45 days after administration, about60 days after administration, about 75 days after administration, orabout 90 days after administration. In other aspects of this embodiment,a sustained release therapeutic compound delivery platform releases atherapeutic compound disclosed herein with substantially first orderrelease kinetics over a period of, e.g., at least 7 days afteradministration, at least 15 days after administration, at least 30 daysafter administration, at least 45 days after administration, at least 60days after administration, at least 75 days after administration, or atleast 90 days after administration.

In aspects of this embodiment, a therapeutic compound delivery platformreleases a therapeutic compound disclosed herein with substantially zeroorder release kinetics over a period of, e.g., about 1 day afteradministration, about 2 days after administration, about 3 days afteradministration, about 4 days after administration, about 5 days afteradministration, or about 6 days after administration. In other aspectsof this embodiment, a therapeutic compound delivery platform releases atherapeutic compound disclosed herein with substantially zero orderrelease kinetics over a period of, e.g., at most 1 day afteradministration, at most 2 days after administration, at most 3 daysafter administration, at most 4 days after administration, at most 5days after administration, or at most 6 days after administration.

In aspects of this embodiment, a therapeutic compound delivery platformreleases a therapeutic compound disclosed herein with substantiallyfirst order release kinetics over a period of, e.g., about 1 day afteradministration, about 2 days after administration, about 3 days afteradministration, about 4 days after administration, about 5 days afteradministration, or about 6 days after administration. In other aspectsof this embodiment, a therapeutic compound delivery platform releases atherapeutic compound disclosed herein with substantially first orderrelease kinetics over a period of, e.g., at most 1 day afteradministration, at most 2 days after administration, at most 3 daysafter administration, at most 4 days after administration, at most 5days after administration, or at most 6 days after administration.

A therapeutic compound disclosed herein may have a log P valueindicating that the compound is soluble in an organic solvent. As usedherein, the term “log P value” refers to the logarithm (base 10) of thepartition coefficient (P) for a compound and is a measure oflipophilicity. Typically, P is defined as the ratio of concentrations ofa unionized compound in the two phases of a mixture of two immisciblesolvents at equilibrium. Thus, log P=Log 10 (P), where P=[solute inimmiscible solvent 1]/[solute in immiscible solvent 2]. With regard toorganic and aqueous phases, the log P value of a compound is constantfor any given pair of aqueous and organic solvents, and its value can bedetermined empirically by one of several phase-partitioning methodsknown to one skilled in the art including, e.g., a shake flask assay, aHPLC assay, and an interface between two immiscible electrolytesolutions (ITIES) assay.

In aspects of this embodiment, a therapeutic compound disclosed hereinmay have a log P value indicating that the compound is substantiallysoluble in an organic solvent. In aspects of this embodiment, atherapeutic compound disclosed herein may have a log P value indicatingthat the compound is, e.g., at least 50% soluble in an organic solvent,at least 60% soluble in an organic solvent, at least 70% soluble in anorganic solvent, at least 80% soluble in an organic solvent, or at least90% soluble in an organic solvent. In aspects of this embodiment, atherapeutic compound disclosed herein may have a log P value indicatingthat the compound is between, e.g., about 50% to about 100% soluble inan organic solvent, about 60% to about 100% soluble in an organicsolvent, about 70% to about 100% soluble in an organic solvent, about80% to about 100% soluble in an organic solvent, or about 90% to about100% soluble in an organic solvent.

In aspects of this embodiment, a therapeutic compound disclosed hereinmay have a log P value of, e.g., more than 1.1, more than 1.2, more than1.4, more than 1.6, more than 1.8, more than 2.0, more than 2.2, morethan 2.4, more than 2.6, more than 2.8, more than 3.0, more than 3.2,more than 3.4, or more than 3.6. In other aspects of this embodiment, atherapeutic compound disclosed herein may have a log P value in therange of, e.g., between 1.8 and 4.0, between 2.0 and 4.0, between 2.1and 4.0, between 2.2 and 4.0, or between 2.3 and 4.0, between 2.4 and4.0, between 2.5 and 4.0, between 2.6 and 4.0, or between 2.8 and 4.0.In other aspects of this embodiment, a therapeutic compound disclosedherein may have a log P value in the range of, e.g., between 3.0 and4.0, or between 3.1 and 4.0, between 3.2 and 4.0, between 3.3 and 4.0,between 3.4 and 4.0, between 3.5 and 4.0, or between 3.6 and 4.0. Instill other aspects of this embodiment, a therapeutic compound disclosedherein may have a log P value in the range of, e.g., between 2.0 and2.5, between 2.0 and 2.7, between 2.0 and 3.0, or between 2.2 and 2.5.

A therapeutic compound disclosed herein may have a polar surface areathat is hydrophobic. As used herein, the term “polar surface area”refers to the surface sum over all of the polar atoms in the structureof a compound and is a measure of hydrophobicity. Typically, these polaratoms include, e.g., oxygen, nitrogen, and their attached hydrogens. Inaspects of this embodiment, a therapeutic compound disclosed herein mayhave a polar surface area of, e.g., less than 8.0 nm², less than 7.0nm², less than 6.0 nm², less than 5.0 nm², less than 4.0 nm², or lessthan 3.0 nm². In other aspects of this embodiment, a therapeuticcompound disclosed herein may have a polar surface area in the range of,e.g., between 3.0 nm² and 6.5 nm², between 3.0 nm² and 6.0 nm², between3.0 nm² and 5.5 nm², between 3.0 nm² and 5.0 nm², between 3.0 nm² and4.5 nm², between 3.5 nm² and 6.5 nm², between 3.5 nm² and 6.0 nm²,between 3.5 nm² and 5.5 nm², between 3.5 nm² and 5.0 nm², between 3.5nm² and 4.5 nm², between 4.0 nm² and 6.5 nm², between 4.0 nm² and 6.0nm², between 4.0 nm² and 5.5 nm², or between 4.0 nm² and 5.0 nm²,between 4.0 nm² and 4.5 nm², or between 4.5 nm² and 5.5 nm². In yetother aspects of this embodiment, a therapeutic compound disclosedherein may have a polar surface area in the range of, e.g., between 2.0nm² and 6.5 nm², between 2.0 nm² and 6.0 nm², between 2.0 nm² and 5.5nm², between 2.0 nm² and 5.0 nm², between 2.0 nm² and 4.5 nm², between2.5 nm² and 6.5 nm², between 2.5 nm² and 6.0 nm², between 2.5 nm² and5.5 nm², between 2.5 nm² and 5.0 nm², or between 2.5 nm² and 4.5 nm².

A therapeutic compound disclosed herein may be an ester of a therapeuticcompound. An ester of a therapeutic compound increases the log P valuerelative to the same therapeutic compound, but without the estermodification. An ester group may be attached to a therapeutic compoundby, e.g., a carboxylic acid or hydroxyl functional group present of thetherapeutic compound. An ester of a therapeutic compound may have anincreased hydrophobicity, and as such, may be dissolved in a reducedvolume of solvent disclosed herein. In some instances, an ester of atherapeutic compound may be combined directly with an adjuvant disclosedherein, thereby eliminating the need of a solvent. An ester of atherapeutic compound may enable the making of a pharmaceuticalcomposition disclosed herein, in situations where a non-esterified formof the same therapeutic compound is otherwise immiscible in a solventdisclosed herein. An ester of a therapeutic compound may still bedelivered in a manner that more effectively inhibits a pro-inflammatoryresponse as long as the compound is combined with an adjuvant disclosedherein. In one embodiment, a therapeutic compound may be reacted withethyl ester in order to form an ethyl ester of the therapeutic compound.

In another embodiment, a pharmaceutical composition disclosed hereindoes not comprise a pharmaceutically-acceptable solvent disclosedherein. In an aspect of this embodiment, a pharmaceutical compositioncomprises a therapeutic compound and a pharmaceutically-acceptableadjuvant, but does not comprise a pharmaceutically-acceptable solventdisclosed herein.

Aspects of the present specification disclose, in part, apharmaceutically-acceptable solvent. A solvent is a liquid, solid, orgas that dissolves another solid, liquid, or gaseous (the solute),resulting in a solution. Solvents useful in the pharmaceuticalcompositions disclosed herein include, without limitation, apharmaceutically-acceptable polar aprotic solvent, apharmaceutically-acceptable polar protic solvent and apharmaceutically-acceptable non-polar solvent. Apharmaceutically-acceptable polar aprotic solvent includes, withoutlimitation, dichloromethane (DCM), tetrahydrofuran (THF), ethyl acetate,acetone, dimethylformamide (DMF), acetonitrile (MeCN), dimethylsulfoxide (DMSO). A pharmaceutically-acceptable polar protic solventincludes, without limitation, acetic acid, formic acid, ethanol,n-butanol, 1-butanol, 2-butanol, isobutanol, sec-butanol, tert-butanol,n-propanol, isopropanol, 1,2 propan-diol, methanol, glycerol, and water.A pharmaceutically-acceptable non-polar solvent includes, withoutlimitation, pentane, cyclopentane, hexane, cyclohexane, benzene,toluene, 1,4-Dioxane, chloroform, n-methyl-pyrrilidone (NMP), anddiethyl ether.

A pharmaceutical composition disclosed herein may comprise a solvent inan amount sufficient to dissolve a therapeutic compound disclosedherein. In other aspects of this embodiment, a pharmaceuticalcomposition disclosed herein may comprise a solvent in an amount of,e.g., less than about 90% (v/v), less than about 80% (v/v), less thanabout 70% (v/v), less than about 65% (v/v), less than about 60% (v/v),less than about 55% (v/v), less than about 50% (v/v), less than about45% (v/v), less than about 40% (v/v), less than about 35% (v/v), lessthan about 30% (v/v), less than about 25% (v/v), less than about 20%(v/v), less than about 15% (v/v), less than about 10% (v/v), less thanabout 5% (v/v), or less than about 1% (v/v). In other aspects of thisembodiment, a pharmaceutical composition disclosed herein may comprise asolvent in an amount in a range of, e.g., about 1% (v/v) to 90% (v/v),about 1% (v/v) to 70% (v/v), about 1% (v/v) to 60% (v/v), about 1% (v/v)to 50% (v/v), about 1% (v/v) to 40% (v/v), about 1% (v/v) to 30% (v/v),about 1% (v/v) to 20% (v/v), about 1% (v/v) to 10% (v/v), about 2% (v/v)to 50% (v/v), about 2% (v/v) to 40% (v/v), about 2% (v/v) to 30% (v/v),about 2% (v/v) to 20% (v/v), about 2% (v/v) to 10% (v/v), about 4% (v/v)to 50% (v/v), about 4% (v/v) to 40% (v/v), about 4% (v/v) to 30% (v/v),about 4% (v/v) to 20% (v/v), about 4% (v/v) to 10% (v/v), about 6% (v/v)to 50% (v/v), about 6% (v/v) to 40% (v/v), about 6% (v/v) to 30% (v/v),about 6% (v/v) to 20% (v/v), about 6% (v/v) to 10% (v/v), about 8% (v/v)to 50% (v/v), about 8% (v/v) to 40% (v/v), about 8% (v/v) to 30% (v/v),about 8% (v/v) to 20% (v/v), about 8% (v/v) to 15% (v/v), or about 8%(v/v) to 12% (v/v).

In one embodiment, a solvent may comprise a pharmaceutically-acceptablealcohol. As used herein, the term “alcohol” refers to an organicmolecule comprising a hydroxyl functional group (OH) bond to a carbonatom, where the carbon atom is saturated. In aspects of this embodiment,the alcohol may be, e.g., a C₂₋₄ alcohol, a C₁₋₄ alcohol, a C₁₋₅alcohol, a C₁₋₇ alcohol, a C₁₋₁₀ alcohol, a C₁₋₁₅ alcohol, or a C₁₋₂₀alcohol. In other aspects of this embodiment, an alcohol may be, e.g., aprimary alcohol, a secondary alcohol, or a tertiary alcohol. In otheraspects of this embodiment, an alcohol may be, e.g., an acyclic alcohol,a monohydric alcohol, a polyhydric alcohol (also known as a polyol orsugar alcohol), an unsaturated aliphatic alcohol, an alicyclic alcohol,or a combination thereof. Examples of a monohydric alcohol include,without limitation, methanol, ethanol, propanol, butanol, pentanol, and1-hexadecanol. Examples of a polyhydric alcohol include, withoutlimitation, glycol, glycerol, arabitol, erythritol, xylitol, maltitol,sorbitol (gluctiol), mannitol, inositol, lactitol, galactitol (iditol),and isomalt. Examples of an unsaturated aliphatic alcohol include,without limitation, prop-2-ene-1-ol, 3,7-dimethylocta-2,6-dien-1-ol, andprop-2-in-1-ol. Examples of an alicyclic alcohol include, withoutlimitation, cyclohexane-1,2,3,4,5,6-hexol and2-(2-propyl)-5-methyl-cyclohexane-1-ol.

In another embodiment, a solvent may comprise an ester ofpharmaceutically-acceptable alcohol and an acid. Suitablepharmaceutically-acceptable alcohols include the ones disclosed herein.Suitable acids include, without limitation, acetic acid, butaric acid,and formic acid. An ester of an alcohol and an acid include, withoutlimitation, methyl acetate, methyl buterate, methyl formate, ethylacetate, ethyl buterate, ethyl formate, propyl acetate, propyl buterate,propyl formate, butyl acetate, butyl buterate, butyl formate, isobutylacetate, isobutyl buterate, isobutyl formate, pentyl acetate, pentylbuterate, pentyl formate, and 1-hexadecyl acetate, 1-hexadecyl buterate,and 1-hexadecyl formate.

In another embodiment, a solvent may comprise apharmaceutically-acceptable glycol ether. Glycol ethers are a group ofsolvents based on alkyl ethers of ethylene glycol. Non-limiting examplesinclude diethylene glycol monomethyl ether (2-(2-methoxyethoxy)ethanol),diethylene glycol monoethyl ether (2-(2-ethoxyethoxy)ethanol),diethylene glycol monopropyl ether (2-(2-propoxyethoxy)ethanol),diethylene glycol monoisopropyl ether (2-(2-isopropoxyethoxy)ethanol),and diethylene glycol mono-n-butyl ether (2-(2-butoxyethoxy)ethanol).Diethylene glycol monoethyl ether (2-(2-ethoxyethoxy)ethanol) iscommercially available as TRANSCUTOL®.

In another embodiment, a solvent may comprise apharmaceutically-acceptable diol. A diol or double alcohol is a chemicalcompound containing two hydroxyl groups (—OH groups).

In another embodiment, a solvent may comprise apharmaceutically-acceptable propylene glycol. Propylene glycol, alsocalled 1,2-propanediol or propane-1,2-diol, is an organic compound withformula C₃H₈O₂ or HO—CH₂—CHOH—CH₃.

In another embodiment, a solvent may comprise apharmaceutically-acceptable dipropylene glycol. Dipropylene glycol is amixture of three isomeric chemical compounds, 4-oxa-2,6-heptandiol,2-(2-Hydroxy-propoxy)-propan-1-ol, and2-(2-Hydroxy-1-methyl-ethoxy)-propan-1-ol.

In another embodiment, a solvent may comprise apharmaceutically-acceptable polypropylene glycol (PPG) polymer. PPGpolymers polymers, also known as polypropylene oxide (PPO) polymers orpolyoxypropylene (POP) polymers, are prepared by polymerization ofpropylene oxide and are commercially available over a wide range ofmolecular weights from 100 g/mol to 10,000,000 g/mol. PPG polymers witha low molecular mass are liquids or low-melting solids, whereas PPGpolymers of a higher molecular mass are solids. A PPG polymer include,without limitation, PPG 100, PPG 200, PPG 300, PPG 400, PPG 500, PPG600, PPG 700, PPG 800, PPG 900, PPG 1000, PPG 1100, PPG 1200, PPG 1300,PPG 1400, PPG 1500, PPG 1600, PPG 1700, PPG 1800, PPG 1900, PPG 2000,PPG 2100, PPG 2200, PPG 2300, PPG 2400, PPG 2500, PPG 2600, PPG 2700,PPG 2800, PPG 2900, PPG 3000, PPG 3250, PPG 3350, PPG 3500, PPG 3750,PPG 4000, PPG 4250, PPG 4500, PPG 4750, PPG 5000, PPG 5500, PPG 6000,PPG 6500, PPG 7000, PPG 7500, PPG 8000, PPG 8500, PPG 9000, PPG 9500,PPG 10,000, PPG 11,000, PPG 12,000, PPG 13,000, PPG 14,000, PPG 15,000,PPG 16,000, PPG 17,000, PPG 18,000, PPG 19,000, or PPG 20,000.

In another embodiment, a solvent may comprise apharmaceutically-acceptable polyethylene glycol (PEG) polymer. PEGpolymers, also known as polyethylene oxide (PEO) polymers orpolyoxyethylene (POE) polymers, are prepared by polymerization ofethylene oxide and are commercially available over a wide range ofmolecular weights from 100 g/mol to 10,000,000 g/mol. PEG polymers witha low molecular mass are liquids or low-melting solids, whereas PEGpolymers of a higher molecular mass are solids. A PEG polymer include,without limitation, PEG 100, PEG 200, PEG 300, PEG 400, PEG 500, PEG600, PEG 700, PEG 800, PEG 900, PEG 1000, PEG 1100, PEG 1200, PEG 1300,PEG 1400, PEG 1500, PEG 1600, PEG 1700, PEG 1800, PEG 1900, PEG 2000,PEG 2100, PEG 2200, PEG 2300, PEG 2400, PEG 2500, PEG 2600, PEG 2700,PEG 2800, PEG 2900, PEG 3000, PEG 3250, PEG 3350, PEG 3500, PEG 3750,PEG 4000, PEG 4250, PEG 4500, PEG 4750, PEG 5000, PEG 5500, PEG 6000,PEG 6500, PEG 7000, PEG 7500, PEG 8000, PEG 8500, PEG 9000, PEG 9500,PEG 10,000, PEG 11,000, PEG 12,000, PEG 13,000, PEG 14,000, PEG 15,000,PEG 16,000, PEG 17,000, PEG 18,000, PEG 19,000, or PEG 20,000.

In another embodiment, a solvent may comprise apharmaceutically-acceptable glyceride. Glycerides comprise a substitutedglycerol, where one, two, or all three hydroxyl groups of the glycerolare each esterified using a fatty acid to produce monoglycerides,diglycerides, and triglycerides, respectively. In these compounds, eachhydroxyl groups of glycerol may be esterified by different fatty acids.Additionally, glycerides may be acetylated to produce acetylatedmonoglycerides, acetylated diglycerides, and acetylated triglycerides.

In one embodiment, a solvent may comprise a pharmaceutically-acceptablesolid solvent. Solid solvents may be useful in the manufacture of asolid dose formulation of a pharmaceutical composition disclosed herein.Typically, a solid solvent is melted in order to dissolve a therapeuticcompound. A pharmaceutically-acceptable solid solvent includes, withoutlimitation, menthol and PEG polymers above about 20,000 g/mol.

Aspects of the present specification disclose, in part, apharmaceutically-acceptable adjuvant. An adjuvant is a pharmacologicalagent that modifies the effect of other agents, such as, e.g., atherapeutic compound disclosed herein. In addition, an adjuvantdisclosed herein may be used as a solvent that dissolves a therapeuticcompound disclosed herein, forming a adjuvant solution. An adjuvantdisclosed herein facilitates delivery of a therapeutic compound in amanner that more effectively inhibits a pro-inflammatory response. Inone embodiment, an adjuvant disclosed herein facilitates the delivery ofa therapeutic compound disclosed herein into macrophages.

A pharmaceutical composition disclosed herein may comprise apharmaceutically-acceptable adjuvant in an amount sufficient to mix witha solution disclosed herein or an emulsion disclosed herein. In otheraspects of this embodiment, a pharmaceutical composition disclosedherein may comprise an adjuvant in an amount of, e.g., at least 10%(v/v), at least 20% (v/v), at least 30% (v/v), at least 35% (v/v), atleast 40% (v/v), at least 45% (v/v), at least 50% (v/v), at least 55%(v/v), at least 60% (v/v), at least 65% (v/v), at least 70% (v/v), atleast 75% (v/v), at least 80% (v/v), at least 85% (v/v), at least 90%(v/v), at least 95% (v/v), or at least 99% (v/v). In other aspects ofthis embodiment, a pharmaceutical composition disclosed herein maycomprise an adjuvant in an amount in a range of, e.g., about 30% (v/v)to about 99% (v/v), about 35% (v/v) to about 99% (v/v), about 40% (v/v)to about 99% (v/v), about 45% (v/v) to about 99% (v/v), about 50% (v/v)to about 99% (v/v), about 30% (v/v) to about 98% (v/v), about 35% (v/v)to about 98% (v/v), about 40% (v/v) to about 98% (v/v), about 45% (v/v)to about 98% (v/v), about 50% (v/v) to about 98% (v/v), about 30% (v/v)to about 95% (v/v), about 35% (v/v) to about 95% (v/v), about 40% (v/v)to about 95% (v/v), about 45% (v/v) to about 95% (v/v), or about 50%(v/v) to about 95% (v/v). In yet other aspects of this embodiment, apharmaceutical composition disclosed herein may comprise an adjuvant inan amount in a range of, e.g., about 70% (v/v) to about 97% (v/v), about75% (v/v) to about 97% (v/v), about 80% (v/v) to about 97% (v/v), about85% (v/v) to about 97% (v/v), about 88% (v/v) to about 97% (v/v), about89% (v/v) to about 97% (v/v), about 90% (v/v) to about 97% (v/v), about75% (v/v) to about 96% (v/v), about 80% (v/v) to about 96% (v/v), about85% (v/v) to about 96% (v/v), about 88% (v/v) to about 96% (v/v), about89% (v/v) to about 96% (v/v), about 90% (v/v) to about 96% (v/v), about75% (v/v) to about 93% (v/v), about 80% (v/v) to about 93% (v/v), about85% (v/v) to about 93% (v/v), about 88% (v/v) to about 93% (v/v), about89% (v/v) to about 93% (v/v), or about 90% (v/v) to about 93% (v/v).

In one embodiment, an adjuvant may be a pharmaceutically-acceptablelipid. A lipid may be broadly defined as a hydrophobic or amphiphilicsmall molecule. The amphiphilic nature of some lipids allows them toform structures such as vesicles, liposomes, or membranes in an aqueousenvironment. Non-limiting examples, of lipids include fatty acids,glycerolipids (like monoglycerides, diglycerides, and triglycerides),phospholipids, sphingolipids, sterol lipids, prenol lipids,saccharolipids, and polyketides. A pharmaceutical composition disclosedherein may comprise a lipid such as, e.g. an oil, an oil-based liquid, afat, a fatty acid, a partially hydrolyzed fatty acid, a wax, a fattyacid ester, a fatty acid salt, a fatty alcohol, a glyceride (mono-, di-or tri-glyceride), a phospholipids, a glycol ester, a sucrose ester, aglycerol oleate derivative, a medium chain triglyceride, a partiallyhydrolyzed triglyceride, or a mixture thereof.

A lipid useful in the pharmaceutical compositions disclosed herein maybe a pharmaceutically-acceptable fatty acid. A fatty acid comprises acarboxylic acid with a long unbranched hydrocarbon chain which may beeither saturated or unsaturated. Thus arrangement confers a fatty acidwith a polar, hydrophilic end, and a nonpolar, hydrophobic end that isinsoluble in water. Most naturally occurring fatty acids have ahydrocarbon chain of an even number of carbon atoms, typically between 4and 24 carbons, and may be attached to functional groups containingoxygen, halogens, nitrogen, and sulfur. Synthetic or non-natural fattyacids may have a hydrocarbon chain of any number of carbon atoms frombetween 3 and 40 carbons. Where a double bond exists, there is thepossibility of either a cis or a trans geometric isomerism, whichsignificantly affects the molecule's molecular configuration. Cis-doublebonds cause the fatty acid chain to bend, an effect that is morepronounced the more double bonds there are in a chain. Most naturallyoccurring fatty acids are of the cis configuration, although the transform does exist in some natural and partially hydrogenated fats andoils. Examples of fatty acids include, without limitation, Capryllicacid (8:0), pelargonic acid (9:0), Capric acid (10:0), Undecylic acid(11:0), Lauric acid (12:0), Tridecylic acid (13:0), Myristic acid(14:0), Myristoleic acid (14:1), Pentadecyclic acid (15:0), Palmiticacid (16:0), Palmitoleic acid (16:1), Sapienic acid (16:1), Margaricacid (17:0), Stearic acid (18:0), Oleic acid (18:1), Elaidic acid(18:1), Vaccenic acid (18:1), Linoleic acid (18:2), Linoelaidic acid(18:2), α-Linolenic acid (18:3), γ-Linolenic acid (18:3), Stearidonicacid (18:4), Nonadecylic acid (19:0), Arachidic acid (20:0), Eicosenoicacid (20:1), Dihomo-γ-linolenic acid (20:3), Mead acid (20:3),Arachidonic acid (20:4), Eicosapentaenoic acid (20:5), Heneicosylic acid(21:0), Behenic acid (22:0), Erucic acid (22:1), Docosahexaenoic acid(22:6), Tricosylic acid (23:0), Lignoceric acid (24:0), Nervonic acid(24:1), Pentacosylic acid (25:0), Cerotic acid (26:0), Heptacosylic acid(27:0), Montanic acid (28:0), Nonacosylic acid (29:0), Melissic acid(30:0), Henatriacontylic acid (31:0), Lacceroic acid (32:0), Psyllicacid (33:0), Geddic acid (34:0), Ceroplastic acid (35:0), andHexatriacontylic acid (36:0).

A lipid useful in the pharmaceutical compositions disclosed herein maybe a pharmaceutically-acceptable partially hydrogenated lipid. Theprocess of hydrogenation adds hydrogen atoms to unsaturated lipid,eliminating double bonds and making them into partially or completelysaturated lipid. Partial hydrogenation is a chemical rather thanenzymatic, that converts a part of cis-isomers into trans-unsaturatedlipids instead of hydrogenating them completely. In the first reactionstep, one hydrogen is added, with the other, coordinatively unsaturated,carbon being attached to the catalyst. The second step is the additionof hydrogen to the remaining carbon, producing a saturated fatty acid.The first step is reversible, such that the hydrogen is readsorbed onthe catalyst and the double bond is re-formed. The intermediate withonly one hydrogen added contains no double bond and can freely rotate.Thus, the double bond can re-form as either cis or trans, of which transis favored, regardless the starting material.

In an embodiment, an adjuvant may be a pharmaceutically-acceptablesaturated or unsaturated fatty acid. In aspects of this embodiment, asaturated or unsaturated fatty acid comprises, e.g., at least 8, atleast 10, at least 12, at least 14, at least 16, at least 18, at least20, at least 22, at least 24, at least 26, at least 28, or at least 30carbon atoms. In other aspects of this embodiment, a saturated orunsaturated fatty acid comprises, e.g., between 4 and 24 carbon atoms,between 6 and 24 carbon atoms, between 8 and 24 carbon atoms, between 10and 24 carbon atoms, between 12 and 24 carbon atoms, between 14 and 24carbon atoms, or between 16 and 24 carbon atoms, between 4 and 22 carbonatoms, between 6 and 22 carbon atoms, between 8 and 22 carbon atoms,between 10 and 22 carbon atoms, between 12 and 22 carbon atoms, between14 and 22 carbon atoms, or between 16 and 22 carbon atoms, between 4 and20 carbon atoms, between 6 and 20 carbon atoms, between 8 and 20 carbonatoms, between 10 and 20 carbon atoms, between 12 and 20 carbon atoms,between 14 and 20 carbon atoms, or between 16 and 20 carbon atoms. Ifunsaturated, the fatty acid may have, e.g., 1 or more, 2 or more, 3 ormore, 4 or more, 5 or more, or 6 or more double bonds.

In aspects of this embodiment, a pharmaceutically-acceptable saturatedor unsaturated fatty acid is liquid at room temperature. The meltingpoint of a fatty acid is largely determined by the degree ofsaturation/unsaturation of the hydrocarbon chain. In aspects of thisembodiment, a saturated or unsaturated fatty acid has a melting pointtemperature of, e.g., 20° C. or below, 15° C. or below, 10° C. or below,5° C. or below, 0° C. or below, −5° C. or below, −10° C. or below, −15°C. or below, or −20° C. or below. In other aspects of this embodiment, asaturated or unsaturated fatty acid has a melting point temperature inthe range of, e.g., about −20° C. to about 20° C., about −20° C. toabout 18° C., about −20° C. to about 16° C., about −20° C. to about 12°C., about −20° C. to about 8° C., about −20° C. to about 4° C., about−20° C. to about 0° C., about −15° C. to about 20° C., about −15° C. toabout 18° C., about −15° C. to about 16° C., about −15° C. to about 12°C., about −15° C. to about 8° C., about −15° C. to about 4° C., about−15° C. to about 0° C.

In another embodiment, an adjuvant may comprise one kind ofpharmaceutically-acceptable fatty acid. In aspects of this embodiment,an adjuvant may comprise only palmitic acid, only stearic acid, onlyoleic acid, only linoleic acid, or only linolenic acid.

In another embodiment, an adjuvant may comprise a plurality of differentpharmaceutically-acceptable fatty acids. In aspects of this embodiment,an adjuvant may comprise, e.g., two or more different fatty acids, threeor more different fatty acids, four or more different fatty acids, fiveor more different fatty acids, or six or more different fatty acids.

In other aspects of this embodiment, an adjuvant may comprise two ormore different pharmaceutically-acceptable fatty acids including atleast palmitic acid, stearic acid, oleic acid, linoleic acid and/orlinolenic acid, and any combination thereof. In other aspects of thisembodiment, an adjuvant may comprise a ratio of palmitic acid and/orstearic acid and/or oleic acid:linolenic acid and/or linoleic acid of,e.g., at least 2:1, at least 3:1, at least 4:1, at least 5:1, at least6:1, at least 7:1, at least 8:1, at least 9:1, at least 10:1, at least15:1, or at least 20:1. In yet other aspects of this embodiment, anadjuvant may comprise a ratio of palmitic acid and/or stearic acidand/or oleic acid:linolenic acid and/or linoleic acid in a range of,e.g., about 1:1 to about 20:1, about 2:1 to about 15:1, about 4:1 toabout 12:1, or about 6:1 to about 10:1.

In other aspects of this embodiment, an adjuvant may comprise four ormore different pharmaceutically-acceptable fatty acids including atleast palmitic acid, stearic acid, oleic acid, linoleic acid and/orlinolenic acid, and any combination thereof. In other aspects of thisembodiment, an adjuvant may comprise a ratio of palmitic acid; stearicacid:linolenic acid:linoleic acid of, e.g., 10:10:1:1, 9:9:1:1, 8:8:1:1,7:7:1:1, 6:6:1:1, 5:5:1:1, 4:4:1:1, 3:3:1:1, 2:2:1:1, or 1:1:1:1. Inother aspects of this embodiment, an adjuvant may comprise a ratio ofpalmitic acid; stearic acid:linolenic acid:linoleic acid in a range of,e.g., about 10:10:1:1 to about 6:6:1:1, about 8:8:1:1 to about 4:4:1:1,or about 5:5:1:1 to about 1:1:1:1.

A lipid useful in the pharmaceutical compositions disclosed herein maybe a pharmaceutically-acceptable omega fatty acid. Non-limiting examplesof an omega fatty acid include omega-3, omega-6, omega-7, and omega-9.Omega-3 fatty acids (also known as n-3 fatty acids or ω-3 fatty acids)are a family of essential unsaturated fatty acids that have in common afinal carbon-carbon double bond in the n-3 position, that is, the thirdbond, counting from the methyl end of the fatty acid. The omega-3 fattyacids are “essential” fatty acids because they are vital for normalmetabolism and cannot be synthesized by the human body. An omega-3 fattyacid includes, without limitation, Hexadecatrienoic acid (16:3),α-Linolenic acid (18:3), Stearidonic acid (18:4), Eicosatrienoic acid(20:3), Eicosatetraenoic acid (20:4), Eicosapentaenoic acid (20:5),Heneicosapentaenoic acid (21:5), Docosapentaenoic acid (Clupanodonicacid) (22:5), Docosahexaenoic acid (22:6), Tetracosapentaenoic acid(24:5), Tetracosahexaenoic acid (Nisinic acid) (24:6).

Omega-6 fatty acids (also known as n-6 fatty acids or ω-6 fatty acids)are a family of unsaturated fatty acids that have in common a finalcarbon-carbon double bond in the n-6 position, that is, the sixth bond,counting from the methyl end of the fatty acid. An omega-6 fatty acidincludes, without limitation, Linoleic acid (18:2), γ-linolenic acid(18:3), Calendic acid (18:3), Eicosadienoic acid (20:2),Dihomo-γ-linolenic acid (20:3), Arachidonic acid (20:4), Docosadienoicacid (22:2), Adrenic acid (22:4), Docosapentaenoic acid (22:5),Tetracosatetraenoic acid (24:4), and Tetracosapentaenoic acid (24:5).

Omega-7 fatty acids (also known as n-7 fatty acids or ω-7 fatty acids)are a family of unsaturated fatty acids that have in common a finalcarbon-carbon double bond in the n-7 position, that is, the seventhbond, counting from the methyl end of the fatty acid. An omega-7 fattyacid includes, without limitation, 5-Dodecenoic acid (12:1),7-Tetradecenoic acid (14:1), 9-Hexadecenoic acid (Palmitoleic acid)(16:1), 11-Decenoic acid (Vaccenic acid) (18:1), 9Z,11E conjugatedLinoleic acid (Rumenic acid)(18:2), 13-Eicosenoic acid (Paullinic acid)(20:1), 15-Docosenoic acid (22:1), and 17-Tetracosenoic acid (24:1).

Omega-9 fatty acids (also known as n-9 fatty acids or ω-9 fatty acids)are a family of unsaturated fatty acids that have in common a finalcarbon-carbon double bond in the n-9 position, that is, the ninth bond,counting from the methyl end of the fatty acid. An omega-9 fatty acidincludes, without limitation, Oleic acid (18:1), Elaidic acid (18:1),Eicosenoic acid (20:1), Mead acid (20:3), Erucic acid (22:1), Nervonicacid (24:1), and Ricinoleic acid.

A lipid useful in the pharmaceutical compositions disclosed herein maybe a pharmaceutically-acceptable fat. Also known as a hard fat or solidfat, a fat includes any fatty acid that is solid at normal roomtemperature, such as, e.g. about 20° C. Fats consist of a wide group ofcompounds that are generally soluble in organic solvents and generallyinsoluble in water. A fat suitable as a lipid useful in thepharmaceutical compositions disclosed herein, may be a triglyceride, atriester of glycerol or any of several fatty acids.

A lipid useful in the pharmaceutical compositions disclosed herein maybe a pharmaceutically-acceptable oil. An oil, also known as a liquidfat, includes any fatty acid that is liquid at normal room temperature,such as, e.g. about 20° C. An oil suitable as a lipid useful in thepharmaceutical compositions disclosed herein, may be a natural oil, avegetable oil or any substance that does not mix with water and has agreasy feel. Examples of suitable natural oils include, withoutlimitation, mineral oil, triacetin, ethyl oleate, a hydrogenated naturaloil, or a mixture thereof. Examples of suitable vegetable oils include,without limitation, almond oil, arachis oil, avocado oil, canola oil,castor oil, coconut oil, corn oil, cottonseed oil, grape seed oil,hazelnut oil, hemp oil, linseed oil (flax seed oil), olive oil, palmoil, peanut oil, rapeseed oil, rice bran oil, safflower oil, sesame oil,soybean oil, soya oil, sunflower oil, theobroma oil (cocoa butter),walnut oil, wheat germ oil, or a mixture thereof. Each of these oils iscommercially available from a number of sources well recognized by thoseskilled in the art.

An oil is typically a mixture of various fatty acids. For example,Rapeseed oil, obtained from the seeds of Brassica napus, includes bothomega-6 and omega-3 fatty acids in a ratio of about 2:1. As anotherexample, linseed oil, obtained from the seeds of Linum usitatissimum,includes abut 7% palmitic acid, about 3.4-4.6% stearic acid, about18.5-22.6% oleic acid, about 14.2-17% linoleic acid, and about51.9-55.2% α-linolenic acid. As another example, theobroma oil, obtainedfrom the seeds of Theobroma cacao, includes glycerides derived frompalmitic acid, stearic acid, oleic acid, linoleic acid, and arichidicacid, with melting point of 34-38° C. In aspects of this embodiment, apharmaceutical composition comprises an oil including at least twodifferent fatty acids, at least three different fatty acids, at leastfour different fatty acids, at least five different fatty acids, or atleast six different fatty acids.

A lipid useful in the pharmaceutical compositions disclosed herein maybe a pharmaceutically-acceptable glycerolipid. Glycerolipids arecomposed mainly of mono-, di-, and tri-substituted glycerols. One groupof glycerolipids is the glycerides, where one, two, or all threehydroxyl groups of glycerol are each esterified using a fatty acid toproduce monoglycerides, diglycerides, and triglycerides, respectively.In these compounds, each hydroxyl groups of glycerol may be esterifiedby different fatty acids. Additionally, glycerides may be acetylated toproduce acetylated monoglycerides, acetylated diglycerides, andacetylated triglycerides. One group of glycerolipids is the glycerides,where one, two, or all three hydroxyl groups of glycerol have sugarresidues attached via a glycosidic linkage.

A lipid useful in the pharmaceutical compositions disclosed herein maybe a pharmaceutically-acceptable glycol fatty acid ester. Apharmaceutically-acceptable glycol fatty acid ester can be a monoesterof a glycol, a diester of a glycol, or a triester of a glycol. A glycolfatty acid ester include, without limitation, a ethylene glycol fattyacid ester, a diethylene glycol fatty acid ester, a propylene glycolfatty acid ester, and a dipropylene fatty acid ester. Non-limitingexamples of glycol fatty acid esters include, e.g., ethylene glycolcaprylate, ethylene glycol pelargonate, ethylene glycol caprate,ethylene glycol undecylate, ethylene glycol laurate, ethylene glycoltridecylate, ethylene glycol myristate, ethylene glycol myristoleate,ethylene glycol pentadecyclate, ethylene glycol palmitate, ethyleneglycol palmitoleate, ethylene glycol sapienate, ethylene glycolmargarate, ethylene glycol stearate, ethylene glycol palmitostearate,ethylene glycol oleate, ethylene glycol elaidate, ethylene glycolvaccinate, ethylene glycol linoleate, ethylene glycol linoelaidate,ethylene glycol α-linolenate, ethylene glycol γ-linolenate, ethyleneglycol stearidonate, ethylene glycol capprylocaprate, ethylene glycoldicapprylocaprate, diethylene glycol caprylate, diethylene glycolpelargonate, diethylene glycol caprate, diethylene glycol undecylate,diethylene glycol laurate, diethylene glycol tridecylate, diethyleneglycol myristate, diethylene glycol myristoleate, diethylene glycolpentadecyclate, diethylene glycol palmitate, diethylene glycolpalmitoleate, diethylene glycol sapienate, diethylene glycol margarate,diethylene glycol stearate, diethylene glycol palmitostearate,diethylene glycol oleate, diethylene glycol elaidate, diethylene glycolvaccinate, diethylene glycol linoleate, diethylene glycol linoelaidate,diethylene glycol α-linolenate, diethylene glycol γ-linolenate,diethylene glycol stearidonate, diethylene glycol capprylocaprate,diethylene glycol dicapprylocaprate, propylene glycol caprylate,propylene glycol pelargonate, propylene glycol caprate, propylene glycolundecylate, propylene glycol laurate, propylene glycol tridecylate,propylene glycol myristate, propylene glycol myristoleate, propyleneglycol pentadecyclate, propylene glycol palmitate, propylene glycolpalmitoleate, propylene glycol sapienate, propylene glycol margarate,propylene glycol stearate, propylene glycol palmitostearate, propyleneglycol oleate, propylene glycol elaidate, propylene glycol vaccinate,propylene glycol linoleate, propylene glycol linoelaidate, propyleneglycol α-linolenate, propylene glycol γ-linolenate, propylene glycolstearidonate, propylene glycol capprylocaprate, propylene glycoldicapprylocaprate, dipropylene glycol caprylate, dipropylene glycolpelargonate, dipropylene glycol caprate, dipropylene glycol undecylate,dipropylene glycol laurate, dipropylene glycol tridecylate, dipropyleneglycol myristate, dipropylene glycol myristoleate, dipropylene glycolpentadecyclate, dipropylene glycol palmitate, dipropylene glycolpalmitoleate, dipropylene glycol sapienate, dipropylene glycolmargarate, dipropylene glycol stearate, dipropylene glycolpalmitostearate, dipropylene glycol oleate, dipropylene glycol elaidate,dipropylene glycol vaccinate, dipropylene glycol linoleate, dipropyleneglycol linoelaidate, dipropylene glycol α-linolenate, dipropylene glycolγ-linolenate, dipropylene glycol stearidonate, dipropylene glycolcapprylocaprate, dipropylene glycol dicapprylocaprate, or anycombination thereof.

A lipid useful in the pharmaceutical compositions disclosed herein maybe a pharmaceutically-acceptable polyether fatty acid ester. Apharmaceutically-acceptable polyether fatty acid ester can be amono-fatty acid ester of a polyether, a di-fatty acid ester of apolyether, or a tri-fatty acid ester of a polyether. A polyether fattyacid ester includes, without limitation, a PEG fatty acid ester, a PEGglyceryl fatty acid, a PEG fatty acid ester glyceride, a PPG fatty acidester, a PPG glyceryl fatty acid, and a PPG fatty acid ester glyceride.A PEG or PPG may be a molecular mass of, e.g., 5-20,000. Non-limitingexamples of polyether fatty acid esters include, e.g., a PEG caprylate,a PEG pelargonate, a PEG caprate, a PEG undecylate, a PEG laurate, a PEGtridecylate, a PEG myristate, a PEG myristoleate, a PEG pentadecyclate,a PEG palmitate, a PEG palmitoleate, a PEG sapienate, a PEG margarate, aPEG stearate, a PEG palmitostearate, PEG oleate, PEG elaidate, PEGvaccinate, PEG linoleate, PEG linoelaidate, PEG α-linolenate, PEGγ-linolenate, PEG stearidonate, PEG capprylocaprate, PEGdicapprylocaprate, a PEG glyceryl caprylate, a PEG glyceryl pelargonate,a PEG glyceryl caprate, a PEG glyceryl undecylate, a PEG glyceryllaurate, a PEG glyceryl tridecylate, a PEG glyceryl myristate, a PEGglyceryl myristoleate, a PEG glyceryl pentadecyclate, a PEG glycerylpalmitate, a PEG glyceryl palmitoleate, a PEG glyceryl sapienate, a PEGglyceryl margarate, a PEG glyceryl stearate, a PEG glycerylpalmitostearate, PEG glyceryl oleate, PEG glyceryl elaidate, PEGglyceryl vaccinate, PEG glyceryl linoleate, PEG glyceryl linoelaidate,PEG glyceryl α-linolenate, PEG glyceryl γ-linolenate, PEG glycerylstearidonate, PEG glyceryl capprylocaprate, PEG glyceryldicapprylocaprate, a capryloyl PEG glyceride, a pelargonoyl PEGglyceride, a caproyl PEG glyceride, an undecyloyl PEG glyceride, alauroyl PEG glyceride, a tridecyloyl PEG glyceride, a myristoyl PEGglyceride, a myristoloyl PEG glyceride, a pentadecycloyl PEG glyceride,a palmitoyl PEG glyceride, a palmitoleoyl PEG glyceride, a sapienoyl PEGglyceride, a margaroyl PEG glyceride, a stearoyl PEG glyceride, apalmitostearoyl PEG glyceride, an oleoyl PEG glyceride, an elaidoyl PEGglyceride, a vaccinoyl PEG glyceride, a linoleoyl PEG glyceride, alinoelaidoyl PEG glyceride, an α-linolenoyl PEG glyceride, aγ-linolenoyl PEG glyceride, a stearidonoyl PEG glyceride, acapprylocaproyl PEG glyceride, a dicapprylocaproyl PEG glyceride, a PPGcaprylate, a PPG pelargonate, a PPG caprate, a PPG undecylate, a PPGlaurate, a PPG tridecylate, a PPG myristate, a PPG myristoleate, a PPGpentadecyclate, a PPG palmitate, a PPG palmitoleate, a PPG sapienate, aPPG margarate, a PPG stearate, a PPG palmitostearate, a PPG oleate, aPPG elaidate, a PPG vaccinate, a PPG linoleate, a PPG linoelaidate, aPPG α-linolenate, a PPG γ-linolenate, a PPG stearidonate, a PPGcapprylocaprate, a PPG dicapprylocaprate, a PPG glyceryl caprylate, aPPG glyceryl pelargonate, a PPG glyceryl caprate, a PPG glycerylundecylate, a PPG glyceryl laurate, a PPG glyceryl tridecylate, a PPGglyceryl myristate, a PPG glyceryl myristoleate, a PPG glycerylpentadecyclate, a PPG glyceryl palmitate, a PPG glyceryl palmitoleate, aPPG glyceryl sapienate, a PPG glyceryl margarate, a PPG glycerylstearate, a PPG glyceryl palmitostearate, a PPG glyceryl oleate, a PPGglyceryl elaidate, a PPG glyceryl vaccinate, a PPG glyceryl linoleate, aPPG glyceryl linoelaidate, a PPG glyceryl α-linolenate, a PPG glycerylγ-linolenate, a PPG glyceryl stearidonate, a PPG glycerylcapprylocaprate, a PPG glyceryl dicapprylocaprate, a capryloyl PPGglyceride, a pelargonoyl PPG glyceride, a caproyl PPG glyceride, anundecyloyl PPG glyceride, a lauroyl PPG glyceride, a tridecyloyl PPGglyceride, a myristoyl PPG glyceride, a myristoloyl PPG glyceride, apentadecycloyl PPG glyceride, a palmitoyl PPG glyceride, a palmitoleoylPPG glyceride, a sapienoyl PPG glyceride, a margaroyl PPG glyceride, astearoyl PPG glyceride, a palmitostearoyl PPG glyceride, an oleoyl PPGglyceride, an elaidoyl PPG glyceride, a vaccinoyl PPG glyceride, alinoleoyl PPG glyceride, a linoelaidoyl PPG glyceride, an α-linolenoylPPG glyceride, a γ-linolenoyl PPG glyceride, a stearidonoyl PPGglyceride, a capprylocaproyl PPG glyceride, a dicapprylocaproyl PPGglyceride, or any combination thereof.

Commercially available pharmaceutically-acceptable polyether fatty acidesters include, without limitation, caprylocaproyl macrogol-8 glycerides(LABRASOL®), propylene glycol monopalmitostearate (MONOSTEOL®), glyceryldibehenate (COMPRITOL® 888), glycerol behenate (COMPRITOL® E ATO),behenoyl pollyoxyl-8 glycerides (COMPRITOL® HD5 ATO), triglyceroldiisostearate (PLUROL® Diisostearique), PEG-8 beeswax (APIFIL®), lauroylmacrogol-32 glycerides (GELUCIRE 44/14), stearoyl macrogol-32 glycerides(GELUCIRE 50.13), propylene glycol dicaprylocaprate (LABRAFAC® PG),polyglycerol-3 dioleate (PLUROL® Oleique CC 497), propylene glycolmonolaurate (type I) (LAUROGLYCOL® FCC), propylene glycol monolaurate(type II) (LAUROGLYCOL® 90), propylene glycol monocaprylate (type I)(CAPRYOL® PGMC), propylene glycol monocaprylate (type II) (CAPRYOL® 90),linoleoyl macrogol-6 glycerides (LABRAFIL® M2125CS), oleoyl macrogol-6glycerides (LABRAFIL® M1944CS), lauroyl macrogol-6 glycerides (LABRAFIL®M2130CS), glycerol dipalmitostearate (Biogapress Vegetal BM297ATO),glycerol distearate (type I) (PRECIROL® ATO 5), and glycerolmonolinoleate (MAISINE™ 35-1).

A lipid useful in the pharmaceutical compositions disclosed herein maybe a mixture of pharmaceutically-acceptable lipids. Examples of mixturesof pharmaceutically-acceptable lipids include, without limitation, amixture of one or more glycerolipids disclosed herein, one or moreglycol fatty acid esters disclosed herein, more polyether fatty acidesters disclosed herein. In aspects of this embodiment, a mixture ofpharmaceutically-acceptable lipids includes a mixture of mono-, di-, andtriglycerides and PEG fatty acid esters having a melting point of about33° C., a mixture of mono-, di-, and triglycerides and PEG fatty acidesters having a melting point of about 35° C., a mixture of mono-, di-,and triglycerides and PEG fatty acid esters having a melting point ofabout 37° C., a mixture of mono-, di-, and triglycerides and PEG fattyacid esters having a melting point of about 39° C., a mixture ofpharmaceutically-acceptable lipids includes mono-, di-, andtriglycerides and PEG fatty acid esters having a melting point of about41° C., a mixture of pharmaceutically-acceptable lipids includes mono-,di-, and triglycerides and PEG fatty acid esters having a melting pointof about 43° C., or a mixture of pharmaceutically-acceptable lipidsincludes mono-, di-, and triglycerides and PEG fatty acid esters havinga melting point of about 45° C. Commercially available mixtures ofpharmaceutically-acceptable lipids include, without limitation, mixturesof PEG-6 sterate and ethylene glycol palmitostearate and PEG-32 stearate(TEFOSE® 1500; TEFOSE® 63), mixtures of triceteareth-4 phosphate andethylene glycol palmitostearate and diethylene glycol palmitostearate(SEDEFOS® 75), mixtures of glycerol monostearate and PEG-75 stearate(GELOT®), mixtures of cetyl alcohol and ethoxylated fatty alcohols(seteth-2-, steareth-20) (EMULCIRE®), mixtures of mono-, di-, andtriglycerides and PEG fatty acid esters having a melting point around33° C. (GELUCIRE® 33/01), mixtures of mono-, di-, and triglycerides andPEG fatty acid esters having a melting point around 39° C. (GELUCIRE®39/01), mixtures of mono-, di-, and triglycerides and PEG fatty acidesters having a melting point around 43° C. (GELUCIRE® 43/01), mixturesof glycerol monostearate 40-55 (type I) and diglycerides (GELEOL® Monoand Diglycerides), and mixtures of medium-chain triglycerides (LABRAFAC®Lipophile WL 1349).

Aspects of the present specification disclose, in part, apharmaceutically-acceptable stabilizing agent. A stabilizing agentreduces or eliminates formation of esters of a therapeutic compound thatmay result as a unwanted reaction with the particular solvent used. Astabilizing agent include, without limitation, water, a sacrificial acidcomprising a fatty acid component and acetic acid, ethyl acetate, asodium acetate/acetic acid (E262), a monoglyceride, an acetylatedmonoglyceride, a diglyceride, an acetylated monoglyceride, an acetylateddiglyceride, a fatty acid, and a fatty acid salt.

In one embodiment, a pharmaceutically-acceptable stabilizing agent maycomprise a pharmaceutically-acceptable emulsifying agent. An emulsifyingagent (also known as an emulgent) is a substance that stabilizes anemulsion comprising a liquid dispersed phase and a liquid continuousphase by increasing its kinetic stability. Thus, in situations where thesolvent and adjuvant used to make a pharmaceutical composition disclosedherein are normally immiscible, an emulsifying agent disclosed herein isused to create a homogenous and stable emulsion. An emulsifying agentincludes, without limitation, a surfactant, a polysaccharide, a lectin,and a phospholipid.

In an aspect of this embodiment, an emulsifying agent may comprise asurfactant. As used hereon, the term “surfactant” refers to a natural orsynthetic amphiphilic compound. A surfactant can be non-ionic,zwitterionic, or ionic. Non-limiting examples of surfactants includepolysorbates like polysorbate 20 (TWEEN® 20), polysorbate 40 (TWEEN®40), polysorbate 60 (TWEEN® 60), polysorbate 61 (TWEEN® 61), polysorbate65 (TWEEN® 65), polysorbate 80 (TWEEN® 80), and polysorbate 81 (TWEEN®81); poloxamers (polyethylene-polypropylene copolymers), like Poloxamer124 (PLURONIC® L44), Poloxamer 181 (PLURONIC® L61), Poloxamer 182(PLURONIC® L62), Poloxamer 184 (PLURONIC® L64), Poloxamer 188 (PLURONIC®F68), Poloxamer 237 (PLURONIC® F87), Poloxamer 338 (PLURONIC® L108),Poloxamer 407 (PLURONIC® F127), polyoxyethyleneglycol dodecyl ethers,like BRIJ® 30, and BRIJ® 35; 2-dodecoxyethanol (LUBROL®-PX);polyoxyethylene octyl phenyl ether (TRITON® X-100); sodium dodecylsulfate (SDS); 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate(CHAPS);3-[(3-Cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate(CHAPSO); sucrose monolaurate; and sodium cholate. Other non-limitingexamples of surfactant excipients can be found in, e.g., Ansel, supra,(1999); Gennaro, supra, (2000); Hardman, supra, (2001); and Rowe, supra,(2003), each of which is hereby incorporated by reference in itsentirety.

In an aspect of this embodiment, an emulsifying agent may comprise apolysaccharide. Non-limiting examples of polysaccharides include guargum, agar, alginate, calgene, a dextran (like dextran 1K, dextran 4K,dextran 40K, dextran 60K, and dextran 70K), dextrin, glycogen, inulin,starch, a starch derivative (like hydroxymethyl starch, hydroxyethylstarch, hydroxypropyl starch, hydroxybutyl starch, and hydroxypentylstarch), hetastarch, cellulose, FICOLL, methyl cellulose (MC),carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC),hydroxypropyl cellulose (HPC), hydroxyethyl methyl cellulose (NEMC),hydroxypropyl methyl cellulose (HPMC); polyvinyl acetates (PVA);polyvinyl pyrrolidones (PVP), also known as povidones, having a K-valueof less than or equal to 18, a K-value greater than 18 or less than orequal to 95, or a K-value greater than 95, like PVP 12 (KOLLIDON® 12),PVP 17 (KOLLIDON® 17), PVP 25 (KOLLIDON® 25), PVP 30 (KOLLIDON® 30), PVP90 (KOLLIDON® 90); and polyethylene imines (PEI).

In an aspect of this embodiment, an emulsifying agent may comprise alectin. Lectins are sugar-binding proteins that are highly specific fortheir sugar moieties. Lectins may be classified according to the sugarmoiety that they bind to, and include, without limitation,mannose-binding lectins, galactose/N-acetylgalactosamine-bindinglectins, N-acetylgluxosamine-binding lectins, N-acetylneuramine-bindinglectins, N-acetylneuraminic acid-binding lectins, and fucose-bindinglectins. Non-limiting examples of surfactants include concanavain A,lentil lectin, snowdrop lectin, Roin, peanut agglutinin, jacain, hairyvetch lectin, wheat germ agglutinin, elderberry lectin, Maackiaanurensis leukoagglutinin, Maackia anurensis hemoagglutinin, Ulexeuropaeus agglutinin, and Aleuria aurantia lectin.

In an aspect of this embodiment, an emulsifying agent may comprise aphospholipid. The structure of the phospholipid generally comprises ahydrophobic tail and a hydrophilic head and is amphipathic in nature.Most phospholipids contain a diglyceride, a phosphate group, and asimple organic molecule such as choline; one exception to this rule issphingomyelin, which is derived from sphingosine instead of glycerol.Phospholipids include, without limitation, diacylglycerides andphosphosphingolipids. Non-limiting examples of diacylglycerides includea phosphatidic acid (phosphatidate) (PA), a phosphatidylethanolamine(cephalin) (PE), a phosphatidylcholine (lecithin) (PC), aphosphatidylserine (PS), and a phosphoinositide includingphosphatidylinositol (PI), phosphatidylinositol phosphate (PIP),phosphatidylinositol bisphosphate (PIP2), and phosphatidylinositoltriphosphate (PIP3). Non-limiting examples of phosphosphingolipidsinclude a ceramide phosphorylcholine (sphingomyelin) (SPH), ceramidephosphorylethanolamine (sphingomyelin) (Cer-PE), and ceramidephosphorylglycerol.

In one embodiment, a pharmaceutically-acceptable stabilizing agent doesnot comprise a pharmaceutically-acceptable emulsifying agent.

In another embodiment, a pharmaceutical composition does not comprise apharmaceutically-acceptable emulsifying agent.

The pharmaceutical compositions disclosed herein act as a deliverysystem that enable a therapeutic compound disclosed herein to be moreeffectively delivered or targeted to a cell type, tissue, organ, orregion of the body in a manner that more effectively inhibits apro-inflammatory response. This inhibition results in an improvedtreatment of a chronic inflammation. For example, a pharmaceuticalcomposition disclosed herein may facilitate the delivery of atherapeutic compound disclosed herein into macrophages. One possiblemechanism that achieves this selective biodistribution is that thepharmaceutical compositions disclosed herein may be designed to takeadvantage of the activity of chylomicrons. Chylomicrons are relativelylarge lipoprotein particles having a diameter of 75 nm to 1,200 nm.Comprising triglycerides (85-92%), phospholipids (6-12%), cholesterol(1-3%) and apolipoproteins (1-2%), chylomicrons transport dietary lipidsfrom the intestines to other locations in the body. Chylomicrons are oneof the five major groups of lipoproteins, the others being VLDL, IDL,low-density lipoproteins (LDL), high-density lipoproteins (HDL), thatenable fats and cholesterol to move within the water-based solution ofthe bloodstream.

During digestion, fatty acids and cholesterol undergo processing in thegastrointestinal tract by the action of pancreatic juices includinglipases and emulsification with bile salts to generate micelles. Thesemicelles allow the absorption of lipid as free fatty acids by theabsorptive cells of the small intestine, known as enterocytes. Once inthe enterocytes, triglycerides and cholesterol are assembled intonascent chylomicrons. Nascent chylomicrons are primarily composed oftriglycerides (85%) and contain some cholesterol and cholesteryl esters.The main apolipoprotein component is apolipoprotein B-48 (APOB48). Thesenascent chylomicrons are released by exocytosis from enterocytes intolacteals, lymphatic vessels originating in the villi of the smallintestine, and are then secreted into the bloodstream at the thoracicduct's connection with the left subclavian vein.

While circulating in lymph and blood, chylomicrons exchange componentswith HDL. The HDL donates apolipoprotein C-II (APOC2) and apolipoproteinE (APOE) to the nascent chylomicron and thus converts it to a maturechylomicron (often referred to simply as “chylomicron”). APOC2 is thecofactor for lipoprotein lipase (LPL) activity. Once triglyceride storesare distributed, the chylomicron returns APOC2 to the HDL (but keepsAPOE), and, thus, becomes a chylomicron remnant, now only 30-50 nm.APOB48 and APOE are important to identify the chylomicron remnant in theliver for endocytosis and breakdown into lipoproteins (VLDL, LDL andHDL). These lipoproteins are processed and stored by competent cells,including, e.g., hepatocytes, adipocytes and macrophages. Thus, withoutwishing to be limited by any theory, upon oral administration, apharmaceutical composition disclosed herein can be processed intomicelles while in the gastrointestinal tract, absorbed by enterocytesand assembled into nascent chylomicrons, remain associated withchylomicron remnants taken up by the liver, and ultimately loaded intomacrophages which are present in inflamed tissues.

As another example, a pharmaceutical composition disclosed herein mayfacilitate the delivery of a therapeutic compound disclosed herein intodentritic cells. One possible mechanism to achieve selectivebiodistribution of the pharmaceutical compositions disclosed herein maybe to take advantage of the endocytotic/phagocytotic activity ofdentritic cells. Dendritic cells are immune cells forming part of themammalian immune system. The main function of dendritic cells is toprocess antigen material and present it on the surface to other cells ofthe immune system. Thus, dendritic cells function as antigen-presentingcells that act as messengers between innate and adaptive immunity.Dendritic cells are present in tissues in contact with the externalenvironment, such as, e.g., the skin (where there is a specializeddendritic cell type called Langerhans cells) and the inner lining of thenose, lungs, stomach and intestines. These cells can also be found in animmature state in the blood. Once activated, they migrate to the lymphnodes where they interact with T cells and B cells to initiate and shapethe adaptive immune response. Dendritic cells are known to endocytoseand phagocytose lipid particles as part of their environmentalmonitoring and antigen presentation processes. Without wishing to belimited by any theory, upon topical or inhalatory administration, apharmaceutical composition disclosed herein can penetrate into the skinor inner lining of the nose, lungs, stomach and intestines, beendocytosed/phagocytosed by dentritic cells, and ultimately loaded intoT cells and/or B cells which are present in inflamed tissues.

Aspects of the present specification disclose, in part, a method ofpreparing a pharmaceutical composition disclosed herein. A methoddisclosed herein comprises the step of contacting apharmaceutically-acceptable adjuvant disclosed herein with a therapeuticcompound disclosed herein under conditions which allow the therapeuticcompound to dissolve in the pharmaceutically-acceptable adjuvant,thereby forming a pharmaceutical composition disclosed herein.

Aspects of the present specification disclose, in part, a method ofpreparing a pharmaceutical composition disclosed herein. A methoddisclosed herein comprises the steps of a) contacting apharmaceutically-acceptable solvent disclosed herein with a therapeuticcompound disclosed herein under conditions which allow the therapeuticcompound to dissolve in the pharmaceutically-acceptable solvent, therebyforming a solution; and b) contacting the solution formed in step (a)with a pharmaceutically-acceptable adjuvant disclosed herein underconditions which allow the formation of a pharmaceutical composition.The methods of preparing disclosed herein may further comprise a step(c) of removing the pharmaceutically-acceptable solvent from thepharmaceutical composition.

The amount of a therapeutic compound that is contacted with thepharmaceutically-acceptable solvent in step (a) of the method may be inany amount desired. Factors used to determine the amount of atherapeutic compound used include, without limitation, the final amountthe therapeutic compound desired in the pharmaceutical composition, thedesired concentration of a therapeutic compound in the solution, thehydrophobicity of the therapeutic compound, the lipophobicity of thetherapeutic compound, the temperature under which the contacting step(a) is performed, and the time under which the contacting step (a) isperformed

The volume of a pharmaceutically-acceptable solvent used in step (a) ofthe method may be any volume desired. Factors used to determine thevolume of a pharmaceutically-acceptable solvent used include, withoutlimitation, the final amount of a pharmaceutical composition desired,the desired concentration of a therapeutic compound in the solution, thehydrophobicity of the therapeutic compound, and the lipophobicity of thetherapeutic compound.

In aspects of this embodiment, the amount of a therapeutic compound thatis contacted with the solvent in step (a) may be, e.g., at least 10 mg,at least 20 mg, at least 30 mg, at least 40 mg, at least 50 mg, at least60 mg, at least 70 mg, at least 80 mg, at least 90 mg, at least 100 mg,at least 200 mg, at least 300 mg, at least 400 mg, at least 500 mg, atleast 600 mg, at least 700 mg, at least 800 mg, at least 900 mg, atleast 1,000 mg, at least 1,100 mg, at least 1,200 mg, at least 1,300 mg,at least 1,400 mg, or at least 1,500 mg. In other aspects of thisembodiment, the amount of a therapeutic compound that is contacted withthe solvent in step (a) may be in the range of, e.g., about 10 mg toabout 100 mg, about 50 mg to about 150 mg, about 100 mg to about 250 mg,about 150 mg to about 350 mg, about 250 mg to about 500 mg, about 350 mgto about 600 mg, about 500 mg to about 750 mg, about 600 mg to about 900mg, about 750 mg to about 1,000 mg, about 850 mg to about 1,200 mg, orabout 1,000 mg to about 1,500 mg. In other aspects of this embodiment,the amount of a therapeutic compound that is dissolved in the solvent instep (a) may be in the range of, e.g., about 10 mg to about 250 mg,about 10 mg to about 500 mg, about 10 mg to about 750 mg, about 10 mg toabout 1,000 mg, about 10 mg to about 1,500 mg, about 50 mg to about 250mg, about 50 mg to about 500 mg, about 50 mg to about 750 mg, about 50mg to about 1,000 mg, about 50 mg to about 1,500 mg, about 100 mg toabout 250 mg, about 100 mg to about 500 mg, about 100 mg to about 750mg, about 100 mg to about 1,000 mg, about 100 mg to about 1,500 mg,about 200 mg to about 500 mg, about 200 mg to about 750 mg, about 200 mgto about 1,000 mg, or about 200 mg to about 1,500 mg.

Step (a) may be carried out at room temperature, in order to allow atherapeutic compound to dissolve fully in thepharmaceutically-acceptable solvent. However, in other embodiments ofthe method, Step (a) may be carried out at a temperature that is greaterthan room temperature. In aspects of this embodiment, Step (a) may becarried out at a temperature that is, e.g., greater than 21° C., greaterthan 25° C., greater than 30° C., greater than 35° C. or greater than37° C., greater than 40° C., greater than 42° C., greater than 45° C.,greater than 50° C., greater than 55° C., or greater than 60° C. Inaspects of this embodiment, Step (a) may be carried out at a temperaturethat is between, e.g., about 20° C. to about 30° C., about 25° C. toabout 35° C., about 30° C. to about 40° C., about 35° C. to about 45°C., about 40° C. to about 50° C., about 45° C. to about 55° C., or about50° C. to about 60° C. In certain cases, Step (a) may be carried out attemperatures below room temperature, in order to allow a therapeuticcompound to dissolve fully in solvent. However, in other embodiments ofthe method, step (a) may be carried out at a temperature that is lessthan room temperature, e.g., less than 10° C., greater than 5° C.,greater than 0° C., greater than −10° C. or greater than −20° C. Thecontacting in Step (a) may comprise mixing the therapeutic compound andthe pharmaceutically-acceptable solvent, e.g., by stirring, inversion,sonication, or vortexing. The mixing may be carried out for, e.g., atleast 1 second, at least 5 seconds, at least 10 seconds, at least 20seconds, at least 30 seconds, at least 45 seconds, at least 60 seconds,or more, until the therapeutic compound is fully dissolved in thesolvent.

After contacting, the concentration of a therapeutic compound disclosedherein in the solution may be in any concentration desired. In aspectsof this embodiment, the concentration of a therapeutic compounddisclosed herein in the solution may be, e.g., at least 0.00001 mg/mL,at least 0.0001 mg/mL, at least 0.001 mg/mL, at least 0.01 mg/mL, atleast 0.1 mg/mL, at least 1 mg/mL, at least 10 mg/mL, at least 25 mg/mL,at least 50 mg/mL, at least 100 mg/mL, at least 200 mg/mL, at least 500mg/mL, at least 700 mg/mL, at least 1,000 mg/mL, or at least 1,200mg/mL. In other aspects of this embodiment, the concentration of atherapeutic compound disclosed herein in the solution may be, e.g., atmost 1,000 mg/mL, at most 1,100 mg/mL, at most 1,200 mg/mL, at most1,300 mg/mL, at most 1,400 mg/mL, at most 1,500 mg/mL, at most 2,000mg/mL, at most 2,000 mg/mL, or at most 3,000 mg/mL. In other aspects ofthis embodiment, the concentration of a therapeutic compound disclosedherein in the solution may be in a range of, e.g., about 0.00001 mg/mLto about 3,000 mg/mL, about 0.0001 mg/mL to about 3,000 mg/mL, about0.01 mg/mL to about 3,000 mg/mL, about 0.1 mg/mL to about 3,000 mg/mL,about 1 mg/mL to about 3,000 mg/mL, about 250 mg/mL to about 3,000mg/mL, about 500 mg/mL to about 3,000 mg/mL, about 750 mg/mL to about3,000 mg/mL, about 1,000 mg/mL to about 3,000 mg/mL, about 100 mg/mL toabout 2,000 mg/mL, about 250 mg/mL to about 2,000 mg/mL, about 500 mg/mLto about 2,000 mg/mL, about 750 mg/mL to about 2,000 mg/mL, about 1,000mg/mL to about 2,000 mg/mL, about 100 mg/mL to about 1,500 mg/mL, about250 mg/mL to about 1,500 mg/mL, about 500 mg/mL to about 1,500 mg/mL,about 750 mg/mL to about 1,500 mg/mL, about 1,000 mg/mL to about 1,500mg/mL, about 100 mg/mL to about 1,200 mg/mL, about 250 mg/mL to about1,200 mg/mL, about 500 mg/mL to about 1,200 mg/mL, about 750 mg/mL toabout 1,200 mg/mL, about 1,000 mg/mL to about 1,200 mg/mL, about 100mg/mL to about 1,000 mg/mL, about 250 mg/mL to about 1,000 mg/mL, about500 mg/mL to about 1,000 mg/mL, about 750 mg/mL to about 1,000 mg/mL,about 100 mg/mL to about 750 mg/mL, about 250 mg/mL to about 750 mg/mL,about 500 mg/mL to about 750 mg/mL, about 100 mg/mL to about 500 mg/mL,about 250 mg/mL to about 500 mg/mL, about 0.00001 mg/mL to about 0.0001mg/mL, about 0.00001 mg/mL to about 0.001 mg/mL, about 0.00001 mg/mL toabout 0.01 mg/mL, about 0.00001 mg/mL to about 0.1 mg/mL, about 0.00001mg/mL to about 1 mg/mL, about 0.001 mg/mL to about 0.01 mg/mL, about0.001 mg/mL to about 0.1 mg/mL, about 0.001 mg/mL to about 1 mg/mL,about 0.001 mg/mL to about 10 mg/mL, or about 0.001 mg/mL to about 100mg/mL.

The volume of a pharmaceutically-acceptable adjuvant used in Step (b) ofthe method may be any volume desired. Factors used to determine thevolume of a pharmaceutically-acceptable adjuvant used include, withoutlimitation, the final amount of a pharmaceutical composition desired,the desired concentration of a therapeutic compound in thepharmaceutical composition, the ratio of solvent:adjuvant used, and themiscibility of solvent and adjuvant.

In aspects of this embodiment, the ratio of solution:adjuvant may be,e.g., at least 5:1, at least 4:1, at least 3:1, at least 2:1, at least0:1, at least 1:1, at least 1:2, at least 1:3, at least 1:4, at least1:5, at least 1:6, at least 1:7, at least 1:8, at least 1:9, at least1:10, at least 1:15, at least 1:20, or at least 1:25. In other aspectsof this embodiment, the ratio of solution:adjuvant may be in a range of,e.g., about 5:1 to about 1:25, about 4:1 to about 1:25, about 3:1 toabout 1:25, about 2:1 to about 1:25, about 0:1 to about 1:25, about 1:1to about 1:25, about 1:2 to about 1:25, about 1:3 to about 1:25, about1:4 to about 1:25, about 1:5 to about 1:25, about 5:1 to about 1:20,about 4:1 to about 1:20, about 3:1 to about 1:20, about 2:1 to about1:20, about 0:1 to about 1:20, about 1:1 to about 1:20, about 1:2 toabout 1:20, about 1:3 to about 1:20, about 1:4 to about 1:20, about 1:5to about 1:20, about 5:1 to about 1:15, about 4:1 to about 1:15, about3:1 to about 1:15, about 0:1 to about 1:15, about 2:1 to about 1:15,about 1:1 to about 1:15, about 1:2 to about 1:15, about 1:3 to about1:15, about 1:4 to about 1:15, about 1:5 to about 1:15, about 5:1 toabout 1:12, about 4:1 to about 1:12, about 3:1 to about 1:12, about 2:1to about 1:12, about 0:1 to about 1:12, about 1:1 to about 1:12, about1:2 to about 1:12, about 1:3 to about 1:12, about 1:4 to about 1:12,about 1:5 to about 1:12, about 1:6 to about 1:12, about 1:7 to about1:12, about 1:8 to about 1:12, about 5:1 to about 1:10, about 4:1 toabout 1:10, about 3:1 to about 1:10, about 2:1 to about 1:10, about 0:1to about 1:10, about 1:1 to about 1:10, about 1:2 to about 1:10, about1:3 to about 1:10, about 1:4 to about 1:10, about 1:5 to about 1:10,about 1:6 to about 1:10, about 1:7 to about 1:10, or about 1:8 to about1:10.

In an embodiment, the ratio of fat:fat, for instance, withoutlimitation, tributyrin, which is an ester composed of butyric acid andglycerol and G43 (a sold fat) may be, e.g., at least 5:1, at least 4:1,at least 3:1, at least 2:1, at least 0:1, at least 1:1, at least 1.1:1,at least 1.2:1, at least 1.3:1, at least 1.4:1, at least 1.5:1, at least1.6:1, at least 1.7:1, at least 1.8:1, at least 1.9:1, at least 1:2, atleast 1:3, at least 1:4, at least 1:5, at least 1:6, at least 1:7, atleast 1:8, at least 1:9, at least 1:10, at least 1:15, at least 1:20, orat least 1:25. In other aspects of this embodiment, the ratio of fat:fatmay be in a range of, e.g., about 5:1 to about 1:25, about 4:1 to about1:25, about 3:1 to about 1:25, about 2:1 to about 1:25, about 0:1 toabout 1:25, about 1:1 to about 1:25, about 1:2 to about 1:25, about 1:3to about 1:25, about 1:4 to about 1:25, about 1:5 to about 1:25, about5:1 to about 1:20, about 4:1 to about 1:20, about 3:1 to about 1:20,about 2:1 to about 1:20, about 0:1 to about 1:20, about 1:1 to about1:20, about 1:2 to about 1:20, about 1:3 to about 1:20, about 1:4 toabout 1:20, about 1:5 to about 1:20, about 5:1 to about 1:15, about 4:1to about 1:15, about 3:1 to about 1:15, about 0:1 to about 1:15, about2:1 to about 1:15, about 1:1 to about 1:15, about 1:2 to about 1:15,about 1:3 to about 1:15, about 1:4 to about 1:15, about 1:5 to about1:15, about 5:1 to about 1:12, about 4:1 to about 1:12, about 3:1 toabout 1:12, about 2:1 to about 1:12, about 0:1 to about 1:12, about 1:1to about 1:12, about 1:2 to about 1:12, about 1:3 to about 1:12, about1:4 to about 1:12, about 1:5 to about 1:12, about 1:6 to about 1:12,about 1:7 to about 1:12, about 1:8 to about 1:12, about 5:1 to about1:10, about 4:1 to about 1:10, about 3:1 to about 1:10, about 2:1 toabout 1:10, about 0:1 to about 1:10, about 1:1 to about 1:10, about 1:2to about 1:10, about 1:3 to about 1:10, about 1:4 to about 1:10, about1:5 to about 1:10, about 1:6 to about 1:10, about 1:7 to about 1:10, orabout 1:8 to about 1:10.

In an embodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in a one fat. In anembodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in two fats. In anembodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in three fats. In anembodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in four fats. In anembodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in five fats. In anembodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in six fats. In anembodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in seven or more fats.

In an embodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in a fat that is aliquid. In an embodiment, a cancer therapeutic, including, withoutlimitation, artemesinin and/or its derivatives is formulated in at fatthat is a solid. In an embodiment, a cancer therapeutic, including,without limitation, artemesinin and/or its derivatives is formulated ina two or more fats that are liquids. In an embodiment, a cancertherapeutic, including, without limitation, artemesinin and/or itsderivatives is formulated in two or more fats that are solids. In anembodiment, a cancer therapeutic, including, without limitation,artemesinin and/or its derivatives is formulated in two or more fats,wherein at least one fat is a solid and at least one fat is a liquid.

Step (b) may be carried out at room temperature, in order to allow thesolution comprising the therapeutic compound to form the pharmaceuticalcomposition. However, in other embodiments of the method, Step (b) maybe carried out at a temperature that is greater than room temperature.In aspects of this embodiment, Step (b) may be carried out at atemperature that is, e.g., greater than 21° C., greater than 25° C.,greater than 30° C., greater than 35° C. or greater than 37° C., greaterthan 40° C., greater than 42° C., greater than 45° C., greater than 50°C., greater than 55° C., or greater than 60° C. In aspects of thisembodiment, Step (a) may be carried out at a temperature that isbetween, e.g., about 20° C. to about 30° C., about 25° C. to about 35°C., about 30° C. to about 40° C., about 35° C. to about 45° C., about40° C. to about 50° C., about 45° C. to about 55° C., or about 50° C. toabout 60° C. In certain cases, Step (b) may be carried out attemperatures below room temperature, in order to allow a therapeuticcompound to dissolve fully in a pharmaceutically-acceptable solvent.However, in other embodiments of the method, step (b) may be carried outat a temperature that is less than room temperature, e.g., less than 10°C., greater than 5° C., greater than 0° C., greater than −10° C. orgreater than −20° C. The contacting in Step (b) may comprise mixing thesolution and the pharmaceutically-acceptable adjuvant, e.g., bystirring, inversion, sonication, or vortexing. The mixing may be carriedout for, e.g., at least 1 second, at least 5 seconds, at least 10seconds, at least 20 seconds, at least 30 seconds, at least 45 seconds,at least 60 seconds, or more, until the pharmaceutical composition isformed.

In certain embodiments, a rapid cooling step may be used to reduce thetemperature of a pharmaceutical composition disclosed herein after itsformation. For example, a rapid cooling step may be used in procedureswere temperatures greater than room temperature are used to allow atherapeutic compound to dissolve fully in thepharmaceutically-acceptable solvent and/or to allow the solutioncomprising the therapeutic compound to form the pharmaceuticalcomposition. In aspects of this embodiment, a rapid cooling step resultsin a temperature decrease of, e.g., about 30° C. in 20 minutes, about25° C. in 20 minutes, about 20° C. in 20 minutes, about 15° C. in 20minutes, about 30° C. in 15 minutes, about 25° C. in 15 minutes, about20° C. in 15 minutes, about 15° C. in 15 minutes, about 30° C. in 10minutes, about 25° C. in 10 minutes, about 20° C. in 10 minutes, about15° C. in 10 minutes, about 30° C. in 5 minutes, about 25° C. in 5minutes, about 20° C. in 5 minutes, about 15° C. in 5 minutes. In otheraspects of this embodiment, a rapid cooling step results in atemperature decrease of, e.g., about 20° C. to about 30° C. in 20minutes, about 20° C. to about 30° C. in 15 minutes, about 20° C. toabout 30° C. in 10 minutes, about 20° C. to about 30° C. in 5 minutes,about 15° C. to about 25° C. in 20 minutes, about 15° C. to about 25° C.in 15 minutes, about 15° C. to about 25° C. in 10 minutes, about 15° C.to about 25° C. in 5 minutes, about 10° C. to about 20° C. in 20minutes, about 10° C. to about 20° C. in 15 minutes, about 10° C. toabout 20° C. in 10 minutes, or about 10° C. to about 20° C. in 5minutes.

In yet aspects of this embodiment, a rapid cooling step results in atemperature decrease of, e.g., about 2.0° C./minute, about 1.9°C./minute, about 1.8° C./minute, about 1.7° C./minute, about 1.6°C./minute, about 1.5° C./minute, about 1.4° C./minute, about 1.3°C./minute, about 1.2° C./minute, about 1.1° C./minute, about 1.0°C./minute, about 0.9° C./minute, about 0.8° C./minute, about 0.7°C./minute, about 0.6° C./minute, about 0.5° C./minute, about 0.4°C./minute, about 0.3° C./minute, about 0.2° C./minute, or about 0.1°C./minute. In still aspects of this embodiment, a rapid cooling stepresults in a temperature decrease of, e.g., about 0.1° C. to about 0.4°C./minute, about 0.2° C. to about 0.6° C./minute, about 0.4° C. to about0.8° C./minute, about 0.6° C. to about 1.0° C./minute, about 0.8° C. toabout 1.2° C./minute, about 1.0° C. to about 1.4° C./minute, about 1.2°C. to about 1.6° C./minute, about 1.4° C. to about 1.8° C./minute, about1.6° C. to about 2.0° C./minute, about 0.1° C. to about 0.5° C./minute,about 0.5° C. to about 1.0° C./minute, about 1.0° C. to about 1.5°C./minute, about 1.5° C. to about 2.0° C./minute, about 0.5° C. to about1.5° C./minute, or about 1.0° C. to about 2.0° C./minute.

In some embodiments, temperatures greater than room temperature employedin either Step (a) or Step (b) or both may be used to remove the solventfrom a pharmaceutical composition. In other embodiment, removal ofsolvent from a pharmaceutical composition requires a separate Step (c).In Step (c), the solvent removal from a pharmaceutical composition maybe accomplished using one of a variety of procedures known in the art,including, without limitation, evaporation, dialyzation, distillation,lypholization, and filtration. These removal procedures may be doneunder conditions of ambient atmosphere, under low pressure, or under avacuum and either at ambient temperature or at temperatures requiringheating.

In one embodiment, Step (c) may result in the complete removal of apharmaceutically-acceptable solvent from the pharmaceutical compositiondisclosed herein. In aspects of this embodiment, Step (c) may result in,e.g., at least 5%, at least 10%, at least 15%, at least 20%, at least25%, at least 30%, at least 35%, at least 40%, at least 45%, at least50%, at least 55%, at least 60%, at least 65%, at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 93%, at least95%, at least 97%, or at least 99% removal of apharmaceutically-acceptable solvent from the pharmaceutical compositiondisclosed herein.

Step (c) is conducted at a temperature that allows for the evaporationof a pharmaceutically-acceptable solvent disclosed herein, and as such,an evaporation temperature is solvent dependant. Factors which influencean evaporation temperature of a solvent disclosed herein include,without limitation, the particular solvent used, the amount of solventpresent, the particular therapeutic compound present, the particularadjuvant present, the stability of the therapeutic compound present, thereactivity of the therapeutic compound present, the particularatmospheric pressure used, the time desired for complete evaporation.Generally, a pharmaceutical composition will require heating if theevaporation step is conducted at ambient pressure, e.g., 1 atm. However,under high vacuum conditions, the evaporation step may be conducted attemperatures below ambient temperature, e.g., less than 22° C.

In one embodiment, removal of solvent from the pharmaceuticalcomposition disclosed herein may be carried out at ambient atmosphericpressure and at a temperature above ambient temperature. In aspects ofthis embodiment, removal of solvent from the pharmaceutical compositiondisclosed herein may be carried out at ambient atmospheric pressure andat a temperature of, e.g., more than 25° C., more than 30° C., more than35° C., more than 40° C., more than 45° C., more than 50° C., more than55° C., more than 60° C., more than 65° C., more than 70° C., more than80° C., or more than 25° C. In other aspects of this embodiment, removalof solvent from the pharmaceutical composition disclosed herein may becarried out at ambient atmospheric pressure and at a temperature in arange of, e.g., about 25° C. to about 100° C., about 25° C. to about 95°C., about 25° C. to about 90° C., about 25° C. to about 85° C., about25° C. to about 80° C., about 25° C. to about 75° C., about 25° C. toabout 70° C., about 25° C. to about 65° C., or about 25° C. to about 60°C.

In another embodiment, removal of solvent from the pharmaceuticalcomposition disclosed herein may be carried out under vacuum and at atemperature below ambient temperature. In aspects of this embodiment,removal of solvent from the pharmaceutical composition disclosed hereinmay be carried out under vacuum and at a temperature of, e.g., less than20° C., less than 18° C., less than 16° C., less than 14° C., less than12° C., less than 10° C., less than 8° C., less than 6° C., less than 4°C., less than 2° C., or less than 0° C. In other aspects of thisembodiment, removal of solvent from the pharmaceutical compositiondisclosed herein may be carried out under vacuum and ata temperature ina range of, e.g., about −20° C. to about 20° C., about −20° C. to about18° C., about −20° C. to about 16° C., about −20° C. to about 14° C.,about −20° C. to about 12° C., about −20° C. to about 10° C., about −20°C. to about 8° C., about −20° C. to about 6° C., about −20° C. to about4° C., about −20° C. to about 2° C., about −20° C. to about 0° C., about−15° C. to about 20° C., about −10° C. to about 20° C., about −5° C. toabout 20° C., about 0° C. to about 20° C., about −10° C. to about 20°C., about −10° C. to about 18° C., about −10° C. to about 16° C., about−10° C. to about 14° C., about −10° C. to about 12° C., about −10° C. toabout 10° C., about −10° C. to about 8° C., about −10° C. to about 6°C., about −10° C. to about 4° C., about −10° C. to about 2° C., or about−10° C. to about 0° C.

The final concentration of a therapeutic compound disclosed herein in apharmaceutical composition disclosed herein may be of any concentrationdesired. In an aspect of this embodiment, the final concentration of atherapeutic compound in a pharmaceutical composition may be atherapeutically effective amount. In other aspects of this embodiment,the final concentration of a therapeutic compound in a pharmaceuticalcomposition may be, e.g., at least 0.00001 mg/mL, at least 0.0001 mg/mL,at least 0.001 mg/mL, at least 0.01 mg/mL, at least 0.1 mg/mL, at least1 mg/mL, at least 10 mg/mL, at least 25 mg/mL, at least 50 mg/mL, atleast 100 mg/mL, at least 200 mg/mL, at least 500 mg/mL, at least 700mg/mL, at least 1,000 mg/mL, or at least 1,200 mg/mL. In other aspectsof this embodiment, the concentration of a therapeutic compounddisclosed herein in the solution may be, e.g., at most 1,000 mg/mL, atmost 1,100 mg/mL, at most 1,200 mg/mL, at most 1,300 mg/mL, at most1,400 mg/mL, at most 1,500 mg/mL, at most 2,000 mg/mL, at most 2,000mg/mL, or at most 3,000 mg/mL. In other aspects of this embodiment, thefinal concentration of a therapeutic compound in a pharmaceuticalcomposition may be in a range of, e.g., about 0.00001 mg/mL to about3,000 mg/mL, about 0.0001 mg/mL to about 3,000 mg/mL, about 0.01 mg/mLto about 3,000 mg/mL, about 0.1 mg/mL to about 3,000 mg/mL, about 1mg/mL to about 3,000 mg/mL, about 250 mg/mL to about 3,000 mg/mL, about500 mg/mL to about 3,000 mg/mL, about 750 mg/mL to about 3,000 mg/mL,about 1,000 mg/mL to about 3,000 mg/mL, about 100 mg/mL to about 2,000mg/mL, about 250 mg/mL to about 2,000 mg/mL, about 500 mg/mL to about2,000 mg/mL, about 750 mg/mL to about 2,000 mg/mL, about 1,000 mg/mL toabout 2,000 mg/mL, about 100 mg/mL to about 1,500 mg/mL, about 250 mg/mLto about 1,500 mg/mL, about 500 mg/mL to about 1,500 mg/mL, about 750mg/mL to about 1,500 mg/mL, about 1,000 mg/mL to about 1,500 mg/mL,about 100 mg/mL to about 1,200 mg/mL, about 250 mg/mL to about 1,200mg/mL, about 500 mg/mL to about 1,200 mg/mL, about 750 mg/mL to about1,200 mg/mL, about 1,000 mg/mL to about 1,200 mg/mL, about 100 mg/mL toabout 1,000 mg/mL, about 250 mg/mL to about 1,000 mg/mL, about 500 mg/mLto about 1,000 mg/mL, about 750 mg/mL to about 1,000 mg/mL, about 100mg/mL to about 750 mg/mL, about 250 mg/mL to about 750 mg/mL, about 500mg/mL to about 750 mg/mL, about 100 mg/mL to about 500 mg/mL, about 250mg/mL to about 500 mg/mL, about 0.00001 mg/mL to about 0.0001 mg/mL,about 0.00001 mg/mL to about 0.001 mg/mL, about 0.00001 mg/mL to about0.01 mg/mL, about 0.00001 mg/mL to about 0.1 mg/mL, about 0.00001 mg/mLto about 1 mg/mL, about 0.001 mg/mL to about 0.01 mg/mL, about 0.001mg/mL to about 0.1 mg/mL, about 0.001 mg/mL to about 1 mg/mL, about0.001 mg/mL to about 10 mg/mL, or about 0.001 mg/mL to about 100 mg/mL.

A pharmaceutical composition produced using the methods disclosed hereinmay be formulated for either local or systemic delivery using topical,enteral or parenteral routes of administration. Additionally, atherapeutic compound disclosed herein may be formulated by itself in apharmaceutical composition, or may be formulated together with one ormore other therapeutic compounds disclosed herein in a singlepharmaceutical composition.

A pharmaceutical composition produced using the methods disclosed hereinmay be a liquid formulation, semi-solid formulation, or a solidformulation. A formulation disclosed herein can be produced in a mannerto form one phase, such as, e.g., an oil or a solid. Alternatively, aformulation disclosed herein can be produced in a manner to form twophase, such as, e.g., an emulsion. A pharmaceutical compositiondisclosed herein intended for such administration may be preparedaccording to any method known to the art for the manufacture ofpharmaceutical compositions. Semi-solid formulations suitable fortopical administration include, without limitation, ointments, creams,salves, and gels.

A liquid formulation may be formed by using various lipids like oils ofother fatty acids that remain as liquids in the temperature rangedesired. In an embodiment, a pharmaceutical composition disclosed hereinis liquid at room temperature. In aspects of this embodiment, apharmaceutical composition disclosed herein may be formulated to be aliquid at a temperature of, e.g., about 25° C. or higher, about 23° C.or higher, about 21° C. or higher, about 19° C. or higher, about 17° C.or higher, about 15° C. or higher, about 12° C. or higher, about 10° C.or higher, about 8° C. or higher, about 6° C. or higher, about 4° C. orhigher, or about 0° C. or higher.

In liquid and semi-solid formulations, a concentration of a therapeuticcompound disclosed herein typically may be between about 50 mg/mL toabout 1,000 mg/mL. In aspects of this embodiment, a therapeuticallyeffective amount of a therapeutic compound disclosed herein may be from,e.g., about 50 mg/mL to about 100 mg/mL, about 50 mg/mL to about 200mg/mL, about 50 mg/mL to about 300 mg/mL, about 50 mg/mL to about 400mg/mL, about 50 mg/mL to about 500 mg/mL, about 50 mg/mL to about 600mg/mL, about 50 mg/mL to about 700 mg/mL, about 50 mg/mL to about 800mg/mL, about 50 mg/mL to about 900 mg/mL, about 50 mg/mL to about 1,000mg/mL, about 100 mg/mL to about 200 mg/mL, about 100 mg/mL to about 300mg/mL, about 100 mg/mL to about 400 mg/mL, about 100 mg/mL to about 500mg/mL, about 100 mg/mL to about 600 mg/mL, about 100 mg/mL to about 700mg/mL, about 100 mg/mL to about 800 mg/mL, about 100 mg/mL to about 900mg/mL, about 100 mg/mL to about 1,000 mg/mL, about 200 mg/mL to about300 mg/mL, about 200 mg/mL to about 400 mg/mL, about 200 mg/mL to about500 mg/mL, about 200 mg/mL to about 600 mg/mL, about 200 mg/mL to about700 mg/mL, about 200 mg/mL to about 800 mg/mL, about 200 mg/mL to about900 mg/mL, about 200 mg/mL to about 1,000 mg/mL, about 300 mg/mL toabout 400 mg/mL, about 300 mg/mL to about 500 mg/mL, about 300 mg/mL toabout 600 mg/mL, about 300 mg/mL to about 700 mg/mL, about 300 mg/mL toabout 800 mg/mL, about 300 mg/mL to about 900 mg/mL, about 300 mg/mL toabout 1,000 mg/mL, about 400 mg/mL to about 500 mg/mL, about 400 mg/mLto about 600 mg/mL, about 400 mg/mL to about 700 mg/mL, about 400 mg/mLto about 800 mg/mL, about 400 mg/mL to about 900 mg/mL, about 400 mg/mLto about 1,000 mg/mL, about 500 mg/mL to about 600 mg/mL, about 500mg/mL to about 700 mg/mL, about 500 mg/mL to about 800 mg/mL, about 500mg/mL to about 900 mg/mL, about 500 mg/mL to about 1,000 mg/mL, about600 mg/mL to about 700 mg/mL, about 600 mg/mL to about 800 mg/mL, about600 mg/mL to about 900 mg/mL, or about 600 mg/mL to about 1,000 mg/mL.

In semi-solid and solid formulations, an amount of a therapeuticcompound disclosed herein typically may be between about 0.01% to about45% by weight. In aspects of this embodiment, an amount of a therapeuticcompound disclosed herein may be from, e.g., about 0.1% to about 45% byweight, about 0.1% to about 40% by weight, about 0.1% to about 35% byweight, about 0.1% to about 30% by weight, about 0.1% to about 25% byweight, about 0.1% to about 20% by weight, about 0.1% to about 15% byweight, about 0.1% to about 10% by weight, about 0.1% to about 5% byweight, about 1% to about 45% by weight, about 1% to about 40% byweight, about 1% to about 35% by weight, about 1% to about 30% byweight, about 1% to about 25% by weight, about 1% to about 20% byweight, about 1% to about 15% by weight, about 1% to about 10% byweight, about 1% to about 5% by weight, about 5% to about 45% by weight,about 5% to about 40% by weight, about 5% to about 35% by weight, about5% to about 30% by weight, about 5% to about 25% by weight, about 5% toabout 20% by weight, about 5% to about 15% by weight, about 5% to about10% by weight, about 10% to about 45% by weight, about 10% to about 40%by weight, about 10% to about 35% by weight, about 10% to about 30% byweight, about 10% to about 25% by weight, about 10% to about 20% byweight, about 10% to about 15% by weight, about 15% to about 45% byweight, about 15% to about 40% by weight, about 15% to about 35% byweight, about 15% to about 30% by weight, about 15% to about 25% byweight, about 15% to about 20% by weight, about 20% to about 45% byweight, about 20% to about 40% by weight, about 20% to about 35% byweight, about 20% to about 30% by weight, about 20% to about 25% byweight, about 25% to about 45% by weight, about 25% to about 40% byweight, about 25% to about 35% by weight, or about 25% to about 30% byweight.

In another embodiment, a solid formulation comprises a cancertherapeutic, including, but not limited to, artemesinin or a derivativethereof, a mixture of mono-, di-, and triglycerides and PEG fatty acidesters, a glyceryl monolinoleate, and a polyethylene glycol. In anaspect of this embodiment, a solid formulation comprises about 1% toabout 30% by weight of a cancer therapeutic, including, but not limitedto, artemesinin or a derivative thereof about 8% to about 70% by weightof a mixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 2% to about 65% by weight of a glyceryl monolinoleate, and about1% to about 15% of polyethylene glycol. In another aspect of thisembodiment, a solid formulation comprises about 10% to about 30% byweight of a cancer therapeutic, including, but not limited to,artemesinin or a derivative thereof about 20% to about 50% by weight ofa mixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 10% to about 30% by weight of a glyceryl monolinoleate, and about5% to about 15% of polyethylene glycol. In yet another aspect of thisembodiment, a solid formulation comprises about 20% to about 30% byweight of a cancer therapeutic, including, but not limited to,artemesinin or a derivative thereof about 30% to about 50% by weight ofa mixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 10% to about 30% by weight of a glyceryl monolinoleate, and about7% to about 13% of polyethylene glycol. In still another aspect of thisembodiment, a solid formulation comprises about 20% to about 30% byweight of a cancer therapeutic, including, but not limited to,artemesinin or a derivative thereof about 35% to about 50% by weight ofa mixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 15% to about 25% by weight of a glyceryl monolinoleate, and about7% to about 13% of polyethylene glycol. In a further aspect of thisembodiment, a solid formulation comprises about 23% to about 27% byweight of a cancer therapeutic, including, but not limited to,artemesinin or a derivative thereof about 41% to about 47% by weight ofa mixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 18% to about 22% by weight of a glyceryl monolinoleate, and about9% to about 11% of polyethylene glycol. In other aspects of thisembodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG 200, a PEG300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In another embodiment, a solid formulation comprises a therapeuticcompound, a hard fat, a partially-hydrogenated fat, a polyethyleneglycol, and a propylene glycol. In an aspect of this embodiment, a solidformulation comprises about 1% to about 30% by weight of therapeuticcompound, about 8% to about 70% by weight of hard fat, about 2% to about65% by weight of partially-hydrogenated fat, about 1% to about 15% ofpolyethylene glycol, and about 1% to about 15% of propylene glycol. Inanother aspect of this embodiment, a solid formulation comprises about10% to about 30% by weight of therapeutic compound, about 20% to about50% by weight of hard fat, about 10% to about 30% by weight ofpartially-hydrogenated fat, about 5% to about 15% of polyethyleneglycol, and about 5% to about 15% of propylene glycol. In yet anotheraspect of this embodiment, a solid formulation comprises about 20% toabout 30% by weight of therapeutic compound, about 30% to about 50% byweight of hard fat, about 10% to about 30% by weight ofpartially-hydrogenated fat, about 7% to about 13% of polyethyleneglycol, and about 7% to about 13% of propylene glycol. In still anotheraspect of this embodiment, a solid formulation comprises about 20% toabout 30% by weight of therapeutic compound, about 35% to about 50% byweight of hard fat, about 15% to about 25% by weight ofpartially-hydrogenated fat, about 7% to about 13% of polyethyleneglycol, and about 7% to about 13% of propylene glycol. In a furtheraspect of this embodiment, a solid formulation comprises about 23% toabout 27% by weight of therapeutic compound, about 41% to about 47% byweight of hard fat, about 18% to about 22% by weight ofpartially-hydrogenated fat, about 9% to about 11% of polyethyleneglycol, and about 9% to about 11% of propylene glycol. In other aspectsof this embodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG200, a PEG 300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In another embodiment, a solid formulation comprises a therapeuticcompound, a mixture of mono-, di-, and triglycerides and PEG fatty acidesters, a glyceryl monolinoleate, a polyethylene glycol, and a propyleneglycol. In an aspect of this embodiment, a solid formulation comprisesabout 1% to about 30% by weight of therapeutic compound, about 8% toabout 70% by weight of a mixture of mono-, di-, and triglycerides andPEG fatty acid esters, about 2% to about 65% by weight of a glycerylmonolinoleate, about 1% to about 15% of polyethylene glycol, and about1% to about 15% of propylene glycol. In another aspect of thisembodiment, a solid formulation comprises about 10% to about 30% byweight of therapeutic compound, about 20% to about 50% by weight of amixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 10% to about 30% by weight of a glyceryl monolinoleate, about 5%to about 15% of polyethylene glycol, and about 5% to about 15% ofpropylene glycol. In yet another aspect of this embodiment, a solidformulation comprises about 20% to about 30% by weight of therapeuticcompound, about 30% to about 50% by weight of a mixture of mono-, di-,and triglycerides and PEG fatty acid esters, about 10% to about 30% byweight of a glyceryl monolinoleate, and about 7% to about 13% ofpolyethylene glycol, and about 7% to about 13% of propylene glycol. Instill another aspect of this embodiment, a solid formulation comprisesabout 20% to about 30% by weight of therapeutic compound, about 35% toabout 50% by weight of a mixture of mono-, di-, and triglycerides andPEG fatty acid esters, about 15% to about 25% by weight of a glycerylmonolinoleate, about 7% to about 13% of polyethylene glycol, and about7% to about 13% of propylene glycol. In a further aspect of thisembodiment, a solid formulation comprises about 23% to about 27% byweight of therapeutic compound, about 41% to about 47% by weight of amixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 18% to about 22% by weight of a glyceryl monolinoleate, about 9%to about 11% of polyethylene glycol, and about 9% to about 11% ofpropylene glycol. In other aspects of this embodiment, a polyethyleneglycol is, e.g., a PEG 100, a PEG 200, a PEG 300, a PEG 400, a PEG 500,a PEG 600, or a PEG 700.

In another embodiment, a solid formulation comprises a cancertherapeutic, including, but not limited to, artemesinin or a derivativethereof, a mixture of mono-, di-, and triglycerides and PEG fatty acidesters, a glyceryl monolinoleate, a polyethylene glycol, and a propyleneglycol. In an aspect of this embodiment, a solid formulation comprisesabout 1% to about 30% by weight of a cancer therapeutic, including, butnot limited to, artemesinin or a derivative thereof, about 8% to about70% by weight of a mixture of mono-, di-, and triglycerides and PEGfatty acid esters, about 2% to about 65% by weight of a glycerylmonolinoleate, about 1% to about 15% of polyethylene glycol, and about1% to about 15% of propylene glycol. In another aspect of thisembodiment, a solid formulation comprises about 10% to about 30% byweight of a cancer therapeutic, including, but not limited to,artemesinin or a derivative thereof, about 20% to about 50% by weight ofa mixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 10% to about 30% by weight of a glyceryl monolinoleate, about 5%to about 15% of polyethylene glycol, and about 5% to about 15% ofpropylene glycol. In yet another aspect of this embodiment, a solidformulation comprises about 20% to about 30% by weight of a cancertherapeutic, including, but not limited to, artemesinin or a derivativethereof, about 30% to about 50% by weight of a mixture of mono-, di-,and triglycerides and PEG fatty acid esters, about 10% to about 30% byweight of a glyceryl monolinoleate, and about 7% to about 13% ofpolyethylene glycol, and about 7% to about 13% of propylene glycol. Instill another aspect of this embodiment, a solid formulation comprisesabout 20% to about 30% by weight of a cancer therapeutic, including, butnot limited to, artemesinin or a derivative thereof, about 35% to about50% by weight of a mixture of mono-, di-, and triglycerides and PEGfatty acid esters, about 15% to about 25% by weight of a glycerylmonolinoleate, about 7% to about 13% of polyethylene glycol, and about7% to about 13% of propylene glycol. In a further aspect of thisembodiment, a solid formulation comprises about 23% to about 27% byweight of a cancer therapeutic, including, but not limited to,artemesinin or a derivative thereof, about 41% to about 47% by weight ofa mixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 18% to about 22% by weight of a glyceryl monolinoleate, about 9%to about 11% of polyethylene glycol, and about 9% to about 11% ofpropylene glycol. In other aspects of this embodiment, a polyethyleneglycol is, e.g., a PEG 100, a PEG 200, a PEG 300, a PEG 400, a PEG 500,a PEG 600, or a PEG 700.

In another embodiment, a semi-solid formulation comprises a therapeuticcompound, a hard fat, a partially-hydrogenated fat, a polyethyleneglycol, and a propylene glycol. In an aspect of this embodiment, asemi-solid formulation comprises about 15% to about 55% by weight oftherapeutic compound, about 7% to about 20% by weight of hard fat, about20% to about 50% by weight of partially-hydrogenated fat, about 7% toabout 20% of polyethylene glycol, and about 1% to about 8% of propyleneglycol. In another aspect of this embodiment, a semi-solid formulationcomprises about 20% to about 50% by weight of therapeutic compound,about 8% to about 18% by weight of hard fat, about 25% to about 45% byweight of partially-hydrogenated fat, about 8% to about 18% ofpolyethylene glycol, and about 2% to about 6% of propylene glycol. Inanother aspect of this embodiment, a semi-solid formulation comprisesabout 20% to about 50% by weight of therapeutic compound, about 10% toabout 16% by weight of hard fat, about 25% to about 45% by weight ofpartially-hydrogenated fat, about 10% to about 16% of polyethyleneglycol, and about 2% to about 6% of propylene glycol. In yet anotheraspect of this embodiment, a semi-solid formulation comprises about 20%to about 50% by weight of therapeutic compound, about 11% to about 15%by weight of hard fat, about 30% to about 40% by weight ofpartially-hydrogenated fat, about 11% to about 15% of polyethyleneglycol, and about 3% to about 5% of propylene glycol. In still anotheraspect of this embodiment, a semi-solid formulation comprises about 25%to about 44% by weight of therapeutic compound, about 12% to about 14%by weight of hard fat, about 32% to about 39% by weight ofpartially-hydrogenated fat, about 12% to about 14% of polyethyleneglycol, and about 4% of propylene glycol. In other aspects of thisembodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG 200, a PEG300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In another embodiment, a semi-solid formulation comprises a therapeuticcompound, a mixture of mono-, di-, and triglycerides and PEG fatty acidesters, a glyceryl monolinoleate, a polyethylene glycol, and a propyleneglycol. In an aspect of this embodiment, a semi-solid formulationcomprises about 15% to about 55% by weight of therapeutic compound,about 7% to about 20% by weight of a mixture of mono-, di-, andtriglycerides and PEG fatty acid esters, about 20% to about 50% byweight of a glyceryl monolinoleate, about 7% to about 20% ofpolyethylene glycol, and about 1% to about 8% of propylene glycol. Inanother aspect of this embodiment, a semi-solid formulation comprisesabout 20% to about 50% by weight of therapeutic compound, about 8% toabout 18% by weight of a mixture of mono-, di-, and triglycerides andPEG fatty acid esters, about 25% to about 45% by weight of a glycerylmonolinoleate, about 8% to about 18% of polyethylene glycol, and about2% to about 6% of propylene glycol. In another aspect of thisembodiment, a semi-solid formulation comprises about 20% to about 50% byweight of therapeutic compound, about 10% to about 16% by weight of amixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 25% to about 45% by weight of a glyceryl monolinoleate, about 10%to about 16% of polyethylene glycol, and about 2% to about 6% ofpropylene glycol. In yet another aspect of this embodiment, a semi-solidformulation comprises about 20% to about 50% by weight of therapeuticcompound, about 11% to about 15% by weight of a mixture of mono-, di-,and triglycerides and PEG fatty acid esters, about 30% to about 40% byweight of a glyceryl monolinoleate, and about 11% to about 15% ofpolyethylene glycol, and about 3% to about 5% of propylene glycol. Instill another aspect of this embodiment, a semi-solid formulationcomprises about 25% to about 44% by weight of therapeutic compound,about 12% to about 14% by weight of a mixture of mono-, di-, andtriglycerides and PEG fatty acid esters, about 32% to about 39% byweight of a glyceryl monolinoleate, about 12% to about 14% ofpolyethylene glycol, and about 4% of propylene glycol. In other aspectsof this embodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG200, a PEG 300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In another embodiment, a semi-solid formulation comprises an ibuprofen,a mixture of mono-, di-, and triglycerides and PEG fatty acid esters, aglyceryl monolinoleate, a polyethylene glycol, and a propylene glycol.In an aspect of this embodiment, a semi-solid formulation comprisesabout 15% to about 55% by weight of an ibuprofen, about 7% to about 20%by weight of a mixture of mono-, di-, and triglycerides and PEG fattyacid esters, about 20% to about 50% by weight of a glycerylmonolinoleate, about 7% to about 20% of polyethylene glycol, and about1% to about 8% of propylene glycol. In another aspect of thisembodiment, a semi-solid formulation comprises about 20% to about 50% byweight of an ibuprofen, about 8% to about 18% by weight of a mixture ofmono-, di-, and triglycerides and PEG fatty acid esters, about 25% toabout 45% by weight of a glyceryl monolinoleate, about 8% to about 18%of polyethylene glycol, and about 2% to about 6% of propylene glycol. Inanother aspect of this embodiment, a semi-solid formulation comprisesabout 20% to about 50% by weight of an ibuprofen, about 10% to about 16%by weight of a mixture of mono-, di-, and triglycerides and PEG fattyacid esters, about 25% to about 45% by weight of a glycerylmonolinoleate, about 10% to about 16% of polyethylene glycol, and about2% to about 6% of propylene glycol. In yet another aspect of thisembodiment, a semi-solid formulation comprises about 20% to about 50% byweight of an ibuprofen, about 11% to about 15% by weight of a mixture ofmono-, di-, and triglycerides and PEG fatty acid esters, about 30% toabout 40% by weight of a glyceryl monolinoleate, and about 11% to about15% of polyethylene glycol, and about 3% to about 5% of propyleneglycol. In still another aspect of this embodiment, a semi-solidformulation comprises about 25% to about 44% by weight of an ibuprofen,about 12% to about 14% by weight of a mixture of mono-, di-, andtriglycerides and PEG fatty acid esters, about 32% to about 39% byweight of a glyceryl monolinoleate, about 12% to about 14% ofpolyethylene glycol, and about 4% of propylene glycol. In other aspectsof this embodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG200, a PEG 300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In another embodiment, a semi-solid formulation comprises a therapeuticcompound, a hard fat, a partially-hydrogenated fat, a polyethyleneglycol, and a propylene glycol. In an aspect of this embodiment, asemi-solid formulation comprises about 10% to about 35% by weight of afree acid of a therapeutic compound, about 1% to about 30% by weight ofa salt of a therapeutic compound, about 7% to about 20% by weight ofhard fat, about 20% to about 50% by weight of partially-hydrogenatedfat, about 7% to about 20% of polyethylene glycol, and about 1% to about8% of propylene glycol. In another aspect of this embodiment, asemi-solid formulation comprises about 15% to about 30% by weight of afree acid of a therapeutic compound, about 1% to about 25% by weight ofa salt of a therapeutic compound, about 10% to about 16% by weight ofhard fat, about 25% to about 45% by weight of partially-hydrogenatedfat, about 10% to about 16% of polyethylene glycol, and about 2% toabout 6% of propylene glycol. In yet another aspect of this embodiment,a semi-solid formulation comprises about 15% to about 30% by weight of afree acid of a therapeutic compound, about 1% to about 25% by weight ofa salt of a therapeutic compound, about 11% to about 15% by weight ofhard fat, about 30% to about 40% by weight of partially-hydrogenatedfat, about 11% to about 15% of polyethylene glycol, and about 3% toabout 5% of propylene glycol. In still another aspect of thisembodiment, a semi-solid formulation comprises about 20% to about 24% byweight of a free acid of a therapeutic compound, about 5% to about 20%by weight of a salt of a therapeutic compound, about 12% to about 14% byweight of hard fat, about 32% to about 39% by weight ofpartially-hydrogenated fat, about 12% to about 14% of polyethyleneglycol, and about 4% of propylene glycol. In other aspects of thisembodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG 200, a PEG300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In another embodiment, a semi-solid formulation comprises a therapeuticcompound, a mixture of mono-, di-, and triglycerides and PEG fatty acidesters, a glyceryl monolinoleate, a polyethylene glycol, and a propyleneglycol. In an aspect of this embodiment, a semi-solid formulationcomprises about 10% to about 35% by weight of a free acid of atherapeutic compound, about 1% to about 30% by weight of a salt of atherapeutic compound, about 7% to about 20% by weight of a mixture ofmono-, di-, and triglycerides and PEG fatty acid esters, about 20% toabout 50% by weight of a glyceryl monolinoleate, about 7% to about 20%of polyethylene glycol, and about 1% to about 8% of propylene glycol. Inanother aspect of this embodiment, a semi-solid formulation comprisesabout 15% to about 30% by weight of a free acid of a therapeuticcompound, about 1% to about 25% by weight of a salt of a therapeuticcompound, about 10% to about 16% by weight of a mixture of mono-, di-,and triglycerides and PEG fatty acid esters, about 25% to about 45% byweight of a glyceryl monolinoleate, about 10% to about 16% ofpolyethylene glycol, and about 2% to about 6% of propylene glycol. Inyet another aspect of this embodiment, a semi-solid formulationcomprises about 15% to about 30% by weight of a free acid of atherapeutic compound, about 1% to about 25% by weight of a salt of atherapeutic compound, about 11% to about 15% by weight of a mixture ofmono-, di-, and triglycerides and PEG fatty acid esters, about 30% toabout 40% by weight of a glyceryl monolinoleate, and about 11% to about15% of polyethylene glycol, and about 3% to about 5% of propyleneglycol. In still another aspect of this embodiment, a semi-solidformulation comprises about 20% to about 24% by weight of a free acid ofa therapeutic compound, about 5% to about 20% by weight of a salt of atherapeutic compound, about 12% to about 14% by weight of a mixture ofmono-, di-, and triglycerides and PEG fatty acid esters, about 32% toabout 39% by weight of a glyceryl monolinoleate, about 12% to about 14%of polyethylene glycol, and about 4% of propylene glycol. In otheraspects of this embodiment, a polyethylene glycol is, e.g., a PEG 100, aPEG 200, a PEG 300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In another embodiment, a semi-solid formulation comprises a cancertherapeutic, including, but not limited to, artemesinin or a derivativethereof, a mixture of mono-, di-, and triglycerides and PEG fatty acidesters, a glyceryl monolinoleate, a polyethylene glycol, and a propyleneglycol. In an aspect of this embodiment, a semi-solid formulationcomprises about 10% to about 35% by weight of a free acid of anibuprofen, about 1% to about 30% by weight of a salt of a cancertherapeutic, including, but not limited to, artemesinin or a derivativethereof, about 7% to about 20% by weight of a mixture of mono-, di-, andtriglycerides and PEG fatty acid esters, about 20% to about 50% byweight of a glyceryl monolinoleate, about 7% to about 20% ofpolyethylene glycol, and about 1% to about 8% of propylene glycol. Inanother aspect of this embodiment, a semi-solid formulation comprisesabout 15% to about 30% by weight of a free acid of a cancer therapeutic,including, but not limited to, artemesinin or a derivative thereof,about 1% to about 25% by weight of a salt of a cancer therapeutic,including, but not limited to, artemesinin or a derivative thereof,about 10% to about 16% by weight of a mixture of mono-, di-, andtriglycerides and PEG fatty acid esters, about 25% to about 45% byweight of a glyceryl monolinoleate, about 10% to about 16% ofpolyethylene glycol, and about 2% to about 6% of propylene glycol. Inyet another aspect of this embodiment, a semi-solid formulationcomprises about 15% to about 30% by weight of a free acid of a cancertherapeutic, including, but not limited to, artemesinin or a derivativethereof, about 1% to about 25% by weight of a salt of an ibuprofen,about 11% to about 15% by weight of a mixture of mono-, di-, andtriglycerides and PEG fatty acid esters, about 30% to about 40% byweight of a glyceryl monolinoleate, and about 11% to about 15% ofpolyethylene glycol, and about 3% to about 5% of propylene glycol. Instill another aspect of this embodiment, a semi-solid formulationcomprises about 20% to about 24% by weight of a free acid of a cancertherapeutic, including, but not limited to, artemesinin or a derivativethereof, about 5% to about 20% by weight of a salt of a cancertherapeutic, including, but not limited to, artemesinin or a derivativethereof about 12% to about 14% by weight of a mixture of mono-, di-, andtriglycerides and PEG fatty acid esters, about 32% to about 39% byweight of a glyceryl monolinoleate, about 12% to about 14% ofpolyethylene glycol, and about 4% of propylene glycol. In other aspectsof this embodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG200, a PEG 300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

A solid or semi-solid formulation disclosed herein takes advantage ofthe different melting point temperatures of the various adjuvants likefatty acids. Formation of a solid or semi-solid dosage form can be bymodifying the respective concentrations of the fatty acids comprising apharmaceutical composition disclosed herein. For example, linolenic acidhas a melting point temperature (T_(m)) of about −11° C., linoleic acidhas a T_(m) of about −5° C., oleic acid has a T_(m) of about 16° C.,palmitic acid has a T_(m) of about 61-62° C., and Stearic acid has aT_(m) of about 67-72° C. Increasing the proportion(s) of palmitic,stearic or oleic acid would increase the overall melting temperature ofa composition, while, conversely, increasing the proportion(s) oflinoleic and linolenic acid would decrease the melting temperature of acomposition. Thus, by controlling the types and amounts of the adjuvantcomponents added, a pharmaceutical composition disclosed herein can bemade that is substantially solid or semi-solid at room temperature, butmelts when it is ingested, and reaches body temperature. The resultingmelted composition readily forms micelles which are absorbed by theintestine, assembled into chylomicrons, and ultimately absorbed bymacrophages. The solid dosage form may be a powder, granule, tablet,capsule or suppository.

In an embodiment, a pharmaceutical composition disclosed herein is solidat room temperature. In aspects of this embodiment, a pharmaceuticalcomposition disclosed herein may be formulated to be a solid at atemperature of, e.g., about 35° C. or lower, about 33° C. or lower,about 31° C. or lower, about 29° C. or lower, about 27° C. or lower,about 25° C. or lower, about 23° C. or lower, about 21° C. or lower,about 19° C. or lower, about 17° C. or lower, about 15° C. or lower,about 12° C. or lower, about 10° C. or lower, about 8° C. or lower,about 6° C. or lower, about 4° C. or lower, or about 0° C. or lower.

In other aspects of this embodiment, a pharmaceutical compositiondisclosed has a melting point temperature of, e.g., 5° C. or higher, 10°C. or higher, 15° C. or higher, 22° C. or higher, 23° C. or higher, 24°C. or higher, 25° C. or higher, 26° C. or higher, 27° C. or higher, 28°C. or higher, 29° C. or higher, 30° C. or higher, 31° C. or higher, 32°C. or higher, 33° C. or higher, 34° C. or higher, or 35° C. or higher.In other aspects of this embodiment, a pharmaceutical compositiondisclosed has a melting point temperature in the range of, e.g., about5° C. to about 24° C., about 10° C. to about 24° C. about 22° C. toabout 24° C., about 23° C. to about 25° C., about 24° C. to about 26°C., about 25° C. to about 27° C., about 26° C. to about 28° C., about27° C. to about 29° C., about 28° C. to about 30° C., about 29° C. toabout 31° C., about 30° C. to about 32° C., about 31° C. to about 33°C., about 32° C. to about 34° C., or about 33° C. to about 35° C. Inother aspects of this embodiment, a pharmaceutical composition disclosedhas a melting point temperature in the range of, e.g., about 22° C. toabout 26° C., about 24° C. to about 28° C., about 26° C. to about 30°C., about 28° C. to about 32° C., or about 30° C. to about 34° C.

In one embodiment, a liquid formulation comprises a therapeuticcompound, a glycol ether, a partially-hydrogenated fat, an oil, and analcohol. In an aspect of this embodiment, a liquid formulation comprisesabout 15% to about 35% by weight of therapeutic compound, about 5% toabout 25% by weight of glycol ether, about 15% to about 40% by weight ofpartially-hydrogenated fat, about 15% to about 40% of an oil, and about1% to about 15% of an alcohol. In another aspect of this embodiment, aliquid formulation comprises about 20% to about 30% by weight oftherapeutic compound, about 10% to about 20% by weight of glycol ether,about 20% to about 35% by weight of partially-hydrogenated fat, about20% to about 35% of an oil, and about 2% to about 10% of an alcohol. Inyet another aspect of this embodiment, a liquid formulation comprisesabout 23% to about 27% by weight of therapeutic compound, about 13% toabout 17% by weight of glycol ether, about 25% to about 30% by weight ofpartially-hydrogenated fat, about 25% to about 30% of an oil, and about4% to about 8% of an alcohol. In still another aspect of thisembodiment, a liquid formulation comprises about 24% to about 26% byweight of therapeutic compound, about 14% to about 16% by weight ofglycol ether, about 26% to about 28% by weight of partially-hydrogenatedfat, about 26% to about 28% of an oil, and about 5% to about 7% of analcohol. In other aspects of this embodiment, an oil is rapeseed oil ortheobroma oil.

In another embodiment, a liquid formulation comprises a therapeuticcompound, a glycol ether, a glyceryl monolinoleate, an oil, and analcohol. In an aspect of this embodiment, a liquid formulation comprisesabout 15% to about 35% by weight of therapeutic compound, about 5% toabout 25% by weight of glycol ether, about 15% to about 40% by weight ofglyceryl monolinoleate, about 15% to about 40% of an oil, and about 1%to about 15% of an alcohol. In another aspect of this embodiment, aliquid formulation comprises about 20% to about 30% by weight oftherapeutic compound, about 10% to about 20% by weight of glycol ether,about 20% to about 35% by weight of glyceryl monolinoleate, about 20% toabout 35% of an oil, and about 2% to about 10% of an alcohol. In yetanother aspect of this embodiment, a liquid formulation comprises about23% to about 27% by weight of therapeutic compound, about 13% to about17% by weight of glycol ether, about 25% to about 30% by weight ofglyceryl monolinoleate, about 25% to about 30% of an oil, and about 4%to about 8% of an alcohol. In still another aspect of this embodiment, aliquid formulation comprises about 24% to about 26% by weight oftherapeutic compound, about 14% to about 16% by weight of glycol ether,about 26% to about 28% by weight of glyceryl monolinoleate, about 26% toabout 28% of an oil, and about 5% to about 7% of an alcohol. In otheraspects of this embodiment, an oil is rapeseed oil or theobroma oil.

In another embodiment, a liquid formulation comprises an ibuprofen, adiethylene glycol monoethyl ether, a glyceryl monolinoleate, an oil, andan alcohol. In an aspect of this embodiment, a liquid formulationcomprises about 15% to about 35% by weight of an ibuprofen, about 5% toabout 25% by weight of diethylene glycol monoethyl ether, about 15% toabout 40% by weight of glyceryl monolinoleate, about 15% to about 40% ofan oil, and about 1% to about 15% of an alcohol. In another aspect ofthis embodiment, a liquid formulation comprises about 20% to about 30%by weight of an ibuprofen, about 10% to about 20% by weight ofdiethylene glycol monoethyl ether, about 20% to about 35% by weight ofglyceryl monolinoleate, about 20% to about 35% of an oil, and about 2%to about 10% of an alcohol. In yet another aspect of this embodiment, aliquid formulation comprises about 23% to about 27% by weight of anibuprofen, about 13% to about 17% by weight of diethylene glycolmonoethyl ether, about 25% to about 30% by weight of glycerylmonolinoleate, about 25% to about 30% of an oil, and about 4% to about8% of an alcohol. In still another aspect of this embodiment, a liquidformulation comprises about 24% to about 26% by weight of an ibuprofen,about 14% to about 16% by weight of diethylene glycol monoethyl ether,about 26% to about 28% by weight of glyceryl monolinoleate, about 26% toabout 28% of an oil, and about 5% to about 7% of an alcohol. In otheraspects of this embodiment, an ibuprofen may be a free acid of a salt ofibuprofen. In other aspects of this embodiment, an oil is rapeseed oilor theobroma oil.

In one embodiment, a liquid formulation comprises a therapeuticcompound, an ester of an alcohol, and an oil. In an aspect of thisembodiment, a liquid formulation comprises about 1% to about 10% byweight of therapeutic compound, about 1% to about 10% by weight of anester of an alcohol, and about 80% to about 98% of an oil. In anotheraspect of this embodiment, a liquid formulation comprises about 2% toabout 8% by weight of therapeutic compound, about 1% to about 7% byweight of an ester of an alcohol, and about 85% to about 97% of an oil.In yet another aspect of this embodiment, a liquid formulation comprisesabout 3% to about 7% by weight of therapeutic compound, about 2% toabout 6% by weight of an ester of an alcohol, and about 87% to about 95%of an oil. In still another aspect of this embodiment, a liquidformulation comprises about 4% to about 6% by weight of therapeuticcompound, about 3% to about 5% by weight of an ester of an alcohol, andabout 90% to about 92% of an oil. In other aspects of this embodiment,an oil is rapeseed oil or theobroma oil.

In another embodiment, a liquid formulation comprises a therapeuticcompound, an ethyl acetate, and an oil. In an aspect of this embodiment,a liquid formulation comprises about 1% to about 10% by weight oftherapeutic compound, about 1% to about 10% by weight of an ethylacetate, and about 80% to about 98% of an oil. In another aspect of thisembodiment, a liquid formulation comprises about 2% to about 8% byweight of therapeutic compound, about 1% to about 7% by weight of anethyl acetate, and about 85% to about 97% of an oil. In yet anotheraspect of this embodiment, a liquid formulation comprises about 3% toabout 7% by weight of therapeutic compound, about 2% to about 6% byweight of an ethyl acetate, and about 87% to about 95% of an oil. Instill another aspect of this embodiment, a liquid formulation comprisesabout 4% to about 6% by weight of therapeutic compound, about 3% toabout 5% by weight of an ethyl acetate, and about 90% to about 92% of anoil. In other aspects of this embodiment, an oil is rapeseed oil ortheobroma oil.

In another embodiment, a liquid formulation comprises an ibuprofen, anethyl acetate, and an oil. In an aspect of this embodiment, a liquidformulation comprises about 1% to about 10% by weight of an ibuprofen,about 1% to about 10% by weight of an ethyl acetate, and about 80% toabout 98% of an oil. In another aspect of this embodiment, a liquidformulation comprises about 2% to about 8% by weight of an ibuprofen,about 1% to about 7% by weight of an ethyl acetate, and about 85% toabout 97% of an oil. In yet another aspect of this embodiment, a liquidformulation comprises about 3% to about 7% by weight of an ibuprofen,about 2% to about 6% by weight of an ethyl acetate, and about 87% toabout 95% of an oil. In still another aspect of this embodiment, aliquid formulation comprises about 4% to about 6% by weight of anibuprofen, about 3% to about 5% by weight of an ethyl acetate, and about90% to about 92% of an oil. In other aspects of this embodiment, anibuprofen may be a free acid of a salt of ibuprofen. In other aspects ofthis embodiment, an oil is rapeseed oil or theobroma oil.

In one embodiment, a solid or semi-solid formulation disclosed herein isformulated without a hydrophilic solvent like water. Such formulationsresult in the formation of co-crystals of the lipids and therapeuticcompound. Stated another way, such formulations do not form liposomalemulsions and/or micellular particles, which require hydrophilicsolvent.

In one embodiment, a solid formulation comprises a therapeutic compound,a hard fat, a partially-hydrogenated fat, and a polyethylene glycol. Inan aspect of this embodiment, a solid formulation comprises about 1% toabout 30% by weight of therapeutic compound, about 8% to about 70% byweight of hard fat, about 2% to about 65% by weight ofpartially-hydrogenated fat, and about 1% to about 15% of polyethyleneglycol. In another aspect of this embodiment, a solid formulationcomprises about 10% to about 30% by weight of therapeutic compound,about 20% to about 50% by weight of hard fat, about 10% to about 30% byweight of partially-hydrogenated fat, and about 5% to about 15% ofpolyethylene glycol. In yet another aspect of this embodiment, a solidformulation comprises about 20% to about 30% by weight of therapeuticcompound, about 30% to about 50% by weight of hard fat, about 10% toabout 30% by weight of partially-hydrogenated fat, and about 7% to about13% of polyethylene glycol. In still another aspect of this embodiment,a solid formulation comprises about 20% to about 30% by weight oftherapeutic compound, about 35% to about 50% by weight of hard fat,about 15% to about 25% by weight of partially-hydrogenated fat, andabout 7% to about 13% of polyethylene glycol. In a further aspect ofthis embodiment, a solid formulation comprises about 23% to about 27% byweight of therapeutic compound, about 41% to about 47% by weight of hardfat, about 18% to about 22% by weight of partially-hydrogenated fat, andabout 9% to about 11% of polyethylene glycol. In other aspects of thisembodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG 200, a PEG300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In another embodiment, a solid formulation comprises a therapeuticcompound, a mixture of mono-, di-, and triglycerides and PEG fatty acidesters, a glyceryl monolinoleate, and a polyethylene glycol. In anaspect of this embodiment, a solid formulation comprises about 1% toabout 30% by weight of therapeutic compound, about 8% to about 70% byweight of a mixture of mono-, di-, and triglycerides and PEG fatty acidesters, about 2% to about 65% by weight of a glyceryl monolinoleate, andabout 1% to about 15% of polyethylene glycol. In another aspect of thisembodiment, a solid formulation comprises about 10% to about 30% byweight of therapeutic compound, about 20% to about 50% by weight of amixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 10% to about 30% by weight of a glyceryl monolinoleate, and about5% to about 15% of polyethylene glycol. In yet another aspect of thisembodiment, a solid formulation comprises about 20% to about 30% byweight of therapeutic compound, about 30% to about 50% by weight of amixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 10% to about 30% by weight of a glyceryl monolinoleate, and about7% to about 13% of polyethylene glycol. In still another aspect of thisembodiment, a solid formulation comprises about 20% to about 30% byweight of therapeutic compound, about 35% to about 50% by weight of amixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 15% to about 25% by weight of a glyceryl monolinoleate, and about7% to about 13% of polyethylene glycol. In a further aspect of thisembodiment, a solid formulation comprises about 23% to about 27% byweight of therapeutic compound, about 41% to about 47% by weight of amixture of mono-, di-, and triglycerides and PEG fatty acid esters,about 18% to about 22% by weight of a glyceryl monolinoleate, and about9% to about 11% of polyethylene glycol. In other aspects of thisembodiment, a polyethylene glycol is, e.g., a PEG 100, a PEG 200, a PEG300, a PEG 400, a PEG 500, a PEG 600, or a PEG 700.

In an embodiment, an artemesinin or a derivative thereof, is linked toan estrogen receptor modulator, including, without limitation, aselective estrogen receptor modulator. In an embodiment the linkage iscovalent bond. In a further embodiment, the linkage is an ionic bond ora non-covalent bond. In an embodiment an artemesinin or a derivativethereof, is linked to an estrogen receptor modulator, including, withoutlimitation, a selective estrogen receptor modulator by a linker. In afurther embodiment, the linker is a chemical linker. In an embodimentthe linker is synthetic, semisynthetic or derived from a naturalproduct.

Aspects of the present specification disclose, in part, reduction ormaintenance of cancer cell population and/or tumor cell size in anindividual. As used herein, the term “treating,” refers to reduction ormaintenance of cancer cell population and/or tumor cell size in anindividual. For example, the term “treating” can mean reduction ormaintenance of cancer cell population and/or tumor cell size levels inan individual by, e.g., at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90% at least 95%, or at least 100%. The actualsymptoms associated with cancer, including the detection of cancer cellpopulation and/or tumor cell size are well known and can be determinedby a person of ordinary skill in the art by using commonly known testingmeans, including blood tests, CT scans sonagrams and other tests knownto those of ordinary skill. Those of skill in the art will know theappropriate symptoms or indicators associated with cancer and will knowhow to determine if an individual is a candidate for treatment asdisclosed herein.

A composition or compound is administered to an individual. Anindividual is typically a human being, but can be an animal, including,but not limited to, dogs, cats, birds, cattle, horses, sheep, goats,reptiles and other animals, whether domesticated or not. Typically, anyindividual who is a candidate for treatment is a candidate with someform of cancer, whether the cancer is benign or malignant, a tumor,solid or otherwise, a cancer call not located in a tumor or some otherform of cancer. Among the most common types of cancer include, but arenot limited to, bladder cancer, breast cancer, colon and rectal cancer,endometrial cancer, kidney cancer, renal cancer, leukemia, lung cancer,melanoma, non-Hodgkins lymphoma, pancreatic cancer, prostate cancer,stomach cancer and thyroid cancer. Pre-operative evaluation typicallyincludes routine history and physical examination in addition tothorough informed consent disclosing all relevant risks and benefits ofthe procedure.

A pharmaceutical composition disclosed herein may comprise a therapeuticcompound in a therapeutically effective amount. As used herein, the term“effective amount” is synonymous with “therapeutically effectiveamount”, “effective dose”, or “therapeutically effective dose” and whenused in reference to reducing or maintaining a cancer cell populationand/or tumor cell size in an individual refers to the minimum dose of atherapeutic compound disclosed herein necessary to achieve the desiredtherapeutic effect and includes a dose sufficient to reduce or maintainof cancer cell population and/or tumor cell size in an individual. Theeffectiveness of a therapeutic compound disclosed herein capable ofreducing or maintaining a cancer cell population and/or tumor cell sizein an individual can be determined by observing an improvement in anindividual based upon one or more clinical symptoms, and/orphysiological indicators associated with reducing or maintaining acancer cell population and/or tumor cell size in an individual.Maintenance or a reduction of cancer cell population and/or tumor cellsize can be indicated by a reduced need for a concurrent therapy. Theeffectiveness of a therapeutic compound disclosed herein capable ofreducing or maintaining a cancer cell population and/or tumor cell sizein an individual can be determined by observing an improvement in anindividual based upon one or more clinical symptoms, and/orphysiological indicators associated with a reduction or maintenance ofcancer cell population and/or tumor cell size.

The appropriate effective amount of a therapeutic compound disclosedherein to be administered to reduce or maintain of a cancer cellpopulation and/or tumor cell size in an individual condition can bedetermined by a person of ordinary skill in the art by taking intoaccount factors, including, without limitation, the measured number ofcancer cells in blood samples or biopsies or CAT scans, PET scans, NMRand/or sonagrams taken from or of the individual, the particularcharacteristics, history and risk factors of the patient, such as, e.g.,age, weight, general health and the like, or any combination thereof.Additionally, where repeated administration of a therapeutic compound isused, an effective amount of a therapeutic compound will further dependupon factors, including, without limitation, the frequency ofadministration, the half-life of the therapeutic compound, or anycombination thereof. In is known by a person of ordinary skill in theart that an effective amount of a therapeutic compound disclosed hereincan be extrapolated from in vitro assays and in vivo administrationstudies using animal models prior to administration to humans oranimals.

Wide variations in the necessary effective amount are to be expected inview of the differing efficiencies of the various routes ofadministration. For instance, oral administration of a therapeuticcompound disclosed herein generally would be expected to require higherdosage levels than administration by inhalation. Similarly, systemicadministration of a therapeutic compound disclosed herein would beexpected to require higher dosage levels than a local administration.Variations in these dosage levels can be adjusted using standardempirical routines of optimization, which are well-known to a person ofordinary skill in the art. The precise therapeutically effective dosagelevels and patterns are preferably determined by the attending physicianin consideration of the above-identified factors. One skilled in the artwill recognize that the condition of the individual can be monitoredthroughout the course of therapy and that the effective amount of atherapeutic compound disclosed herein that is administered can beadjusted accordingly.

In an embodiment, in instances in which each of the therapeuticcompounds themselves are administered, without limitation, as individualor separate dosage forms (e.g., capsules or tablets), the kit comprises,without limitation, each of the therapeutic compounds making up thecomposition of the invention, along with instructions for use. In anadditional embodiment, the therapeutic compound components, withoutlimitation, may be packaged in any manner suitable for administration,so long as the packaging, when considered along with the instructionsfor administration, without limitation, clearly indicates the manner inwhich each of the therapeutic compound components is to be administered.In a further embodiment, each of the therapeutic compounds or acombination of such therapeutic compounds may, without limitation, becombined into a single administrable dosage form such as a capsule,tablet, or other solid or liquid formulation. The therapeutic compoundcan be provided to an individual in a package. The package can be acontainer, for instance, without limitation, a bottle, a canister, atube or other enclosed vessel. The package can also be a packet, such asa blister pack.

In an embodiment, the individual or separate dosage is in the form of ablister pack. In an aspect of this embodiment, a blister pack is a termfor several types of pre-formed plastic packaging used for smallconsumer goods, foods, and for pharmaceuticals. In a further embodiment,a blister pack is comprised of a cavity or pocket made from a formableweb, usually a thermoformed plastic and typically includes a backing ofpaperboard or a lidding seal of aluminum foil or plastic. In a furtherembodiment, a blister that folds onto itself is a clamshell. In anaspect of this embodiment, a blister pack is commonly used as unit-dosepackaging for pharmaceutical tablets, capsules or lozenges. In anembodiment, a blister pack can provide barrier protection for shelf liferequirements, and a degree of tamper resistance and can be used forpacking physician samples of therapeutic compound products or for OverThe Counter (OTC) products in the pharmacy.

In an embodiment, an individual is provided a treatment protocol whereina pharmaceutical composition is administered on a periodic schedule,wherein the individual is informed by electronic notification toadminister the therapeutic compound so that the individual is remindedto take the therapeutic compound on a period schedule. In an aspect ofthis embodiment, the electronic notification is by email, text, instantmessaging or by another electronic notification method. In anembodiment, an individual is informed to administer the therapeuticcompound on a period schedule through receipt of a telephone call,postal mail, overnight express (including, without limitation, FedEx andUPS) or other method of notification.

In an embodiment, the effectiveness of a cancer therapeutic to killcancer cells or reduce tumor size is enhanced through the formulation ofthe cancer therapeutic with one or more fats as compared to the samecancer therapeutic not formulated in a fat. In a further embodiment, theeffectiveness of a cancer therapeutic to kill cancer cells or reducetumor size is enhanced through the formulation of the cancer therapeuticwith one or more fats, wherein at least one fat is a solid fat. In anembodiment, the effectiveness of a cancer therapeutic to kill cancercells or reduce tumor size is enhanced through the formulation of thecancer therapeutic with one or more fats, wherein at least one fat is aliquid. In an embodiment, the effectiveness of a cancer therapeutic,including, without limitation, artemesinin and/or a derivative thereof,to kill cancer cells or reduce tumor size is enhanced through theformulation of the cancer therapeutic with one or more fats as comparedto the same cancer therapeutic not formulated in a fat.

In aspects of this embodiment, a therapeutically effective amount of atherapeutic compound disclosed herein reduces or maintains a cancer cellpopulation and/or tumor cell size in an individual by, e.g., at least10%, at least 15%, at least 20%, at least 25%, at least 30%, at least35%, at least 40%, at least 45%, at least 50%, at least 55%, at least60%, at least 65%, at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95% or at least 100%. In other aspects ofthis embodiment, a therapeutically effective amount of a therapeuticcompound disclosed herein reduces or maintains a cancer cell populationand/or tumor cell size in an individual by, e.g., at most 10%, at most15%, at most 20%, at most 25%, at most 30%, at most 35%, at most 40%, atmost 45%, at most 50%, at most 55%, at most 60%, at most 65%, at most70%, at most 75%, at most 80%, at most 85%, at most 90%, at most 95% orat most 100%. In yet other aspects of this embodiment, a therapeuticallyeffective amount of a therapeutic compound disclosed herein reduces ormaintains a cancer cell population and/or tumor cell size in anindividual by, e.g., about 10% to about 100%, about 10% to about 90%,about 10% to about 80%, about 10% to about 70%, about 10% to about 60%,about 10% to about 50%, about 10% to about 40%, about 20% to about 100%,about 20% to about 90%, about 20% to about 80%, about 20% to about 20%,about 20% to about 60%, about 20% to about 50%, about 20% to about 40%,about 30% to about 100%, about 30% to about 90%, about 30% to about 80%,about 30% to about 70%, about 30% to about 60%, or about 30% to about50%.

In other aspects of this embodiment, a therapeutically effective amountof a therapeutic compound disclosed herein generally is in the range ofabout 0.001 mg/kg/day to about 100 mg/kg/day. In aspects of thisembodiment, an effective amount of a therapeutic compound disclosedherein may be, e.g., at least 0.001 mg/kg/day, at least 0.01 mg/kg/day,at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day,at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, atleast 25 mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, atleast 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day. Inother aspects of this embodiment, an effective amount of a therapeuticcompound disclosed herein may be in the range of, e.g., about 0.001mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/day to about 15mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day, about 0.001mg/kg/day to about 25 mg/kg/day, about 0.001 mg/kg/day to about 30mg/kg/day, about 0.001 mg/kg/day to about 35 mg/kg/day, about 0.001mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to about 45mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day to about 100mg/kg/day. In yet other aspects of this embodiment, an effective amountof a therapeutic compound disclosed herein may be in the range of, e.g.,about 0.01 mg/kg/day to about 10 mg/kg/day, about 0.01 mg/kg/day toabout 15 mg/kg/day, about 0.01 mg/kg/day to about 20 mg/kg/day, about0.01 mg/kg/day to about 25 mg/kg/day, about 0.01 mg/kg/day to about 30mg/kg/day, about 0.01 mg/kg/day to about 35 mg/kg/day, about 0.01mg/kg/day to about 40 mg/kg/day, about 0.01 mg/kg/day to about 45mg/kg/day, about 0.01 mg/kg/day to about 50 mg/kg/day, about 0.01mg/kg/day to about 75 mg/kg/day, or about 0.01 mg/kg/day to about 100mg/kg/day. In still other aspects of this embodiment, an effectiveamount of a therapeutic compound disclosed herein may be in the rangeof, e.g., about 0.1 mg/kg/day to about 10 mg/kg/day, about 0.1 mg/kg/dayto about 15 mg/kg/day, about 0.1 mg/kg/day to about 20 mg/kg/day, about0.1 mg/kg/day to about 25 mg/kg/day, about 0.1 mg/kg/day to about 30mg/kg/day, about 0.1 mg/kg/day to about 35 mg/kg/day, about 0.1mg/kg/day to about 40 mg/kg/day, about 0.1 mg/kg/day to about 45mg/kg/day, about 0.1 mg/kg/day to about 50 mg/kg/day, about 0.1mg/kg/day to about 75 mg/kg/day, or about 0.1 mg/kg/day to about 100mg/kg/day.

In other aspects of this embodiment, an effective amount of atherapeutic compound disclosed herein may be in the range of, e.g.,about 1 mg/kg/day to about 10 mg/kg/day, about 1 mg/kg/day to about 15mg/kg/day, about 1 mg/kg/day to about 20 mg/kg/day, about 1 mg/kg/day toabout 25 mg/kg/day, about 1 mg/kg/day to about 30 mg/kg/day, about 1mg/kg/day to about 35 mg/kg/day, about 1 mg/kg/day to about 40mg/kg/day, about 1 mg/kg/day to about 45 mg/kg/day, about 1 mg/kg/day toabout 50 mg/kg/day, about 1 mg/kg/day to about 75 mg/kg/day, or about 1mg/kg/day to about 100 mg/kg/day. In yet other aspects of thisembodiment, an effective amount of a therapeutic compound disclosedherein may be in the range of, e.g., about 5 mg/kg/day to about 10mg/kg/day, about 5 mg/kg/day to about 15 mg/kg/day, about 5 mg/kg/day toabout 20 mg/kg/day, about 5 mg/kg/day to about 25 mg/kg/day, about 5mg/kg/day to about 30 mg/kg/day, about 5 mg/kg/day to about 35mg/kg/day, about 5 mg/kg/day to about 40 mg/kg/day, about 5 mg/kg/day toabout 45 mg/kg/day, about 5 mg/kg/day to about 50 mg/kg/day, about 5mg/kg/day to about 75 mg/kg/day, or about 5 mg/kg/day to about 100mg/kg/day.

In other aspects of this embodiment, a therapeutically effective amountof a therapeutic compound disclosed herein generally is in the range ofabout 1 mg/day to about 3,000 mg/day. In aspects of this embodiment, aneffective amount of a therapeutic compound disclosed herein may be,e.g., at least 1 mg/day, at least 5 mg/day, at least 10 mg/day, at least15 mg/day, at least 20 mg/day, at least 25 mg/day, at least 30 mg/day,at least 40 mg/day, at least 50 mg/day, at least 100 mg/day, at least150 mg/day, at least 200 mg/day, at least 250 mg/day, at least 300mg/day, at least 350 mg/day, at least 400 mg/day, at least 450 mg/day,at least 500 mg/day, at least 550 mg/day, at least 600 mg/day, at least650 mg/day, at least 700 mg/day, at least 750 mg/day, at least 800mg/day, at least 850 mg/day, at least 900 mg/day, at least 950 mg/day,at least 1,000 mg/day, at least 1.50 mg/day, at least 1,100 mg/day, atleast 1,150 mg/day, at least 1,200 mg/day, at least 1,250 mg/day, atleast 1,300 mg/day, at least 1,350 mg/day, at least 1,400 mg/day, atleast 1,450 mg/day, at least 1,500 mg/day, at least 1,600 mg/day, atleast 1,700 mg/day, at least 1,800 mg/day, at least 1,900 mg/day, atleast 2,000 mg/day, at least 2,100 mg/day, at least 2,200 mg/day, atleast 2,300 mg/day, at least 2,400 mg/day, at least 2,500 mg/day, atleast 2,600 mg/day, at least 2,700 mg/day, at least 2,800 mg/day, atleast 2,900 mg/day, or at least 3,000 mg/day. In yet other aspects ofthis embodiment, an effective amount of a therapeutic compound disclosedherein may be between, e.g., about 1 mg/day to about 1,000 mg/day, about5 mg/day to about 1,000 mg/day, about 10 mg/day to about 1,000 mg/day,about 15 mg/day to about 1,000 mg/day, about 20 mg/day to about 1,000mg/day, about 25 mg/day to about 1,000 mg/day, about 30 mg/day to about1,000 mg/day, about 40 mg/day to about 1,000 mg/day, about 50 mg/day toabout 1,000 mg/day, about 100 mg/day to about 1,000 mg/day, about 150mg/day to about 1,000 mg/day, about 200 mg/day to about 1,000 mg/day,about 250 mg/day to about 1,000 mg/day, about 300 mg/day to about 1,000mg/day, about 350 mg/day to about 1,000 mg/day, about 400 mg/day toabout 1,000 mg/day, about 450 mg/day to about 1,000 mg/day, about 500mg/day to about 1,000 mg/day, about 50 mg/day to about 1,500 mg/day,about 100 mg/day to about 1,500 mg/day, about 150 mg/day to about 1,500mg/day, about 200 mg/day to about 1,500 mg/day, about 250 mg/day toabout 1,500 mg/day, about 300 mg/day to about 1,500 mg/day, about 350mg/day to about 1,500 mg/day, about 400 mg/day to about 1,500 mg/day,about 450 mg/day to about 1,500 mg/day, about 500 mg/day to about 1,500mg/day, about 1,000 mg/day to about 3,000 mg/day, about 1,100 mg/day toabout 3,000 mg/day, about 1,200 mg/day to about 3,000 mg/day, about1,3000 mg/day to about 3,000 mg/day, about 1,400 mg/day to about 3,000mg/day, about 1,500 mg/day to about 3,000 mg/day, about 1,600 mg/day toabout 3,000 mg/day, about 1,700 mg/day to about 3,000 mg/day, about1,800 mg/day to about 3,000 mg/day, about 1,900 mg/day to about 3,000mg/day, or about 2,000 mg/day to about 3,000 mg/day.

In other aspects of this embodiment, a therapeutically effective amountof a artemesinin and/or a derivative thereof disclosed herein generallyis in the range of about 0.001 mg/kg/day to about 100 mg/kg/day. Inaspects of this embodiment, an effective amount of a statin disclosedherein may be, e.g., at least 0.001 mg/kg/day, at least 0.01 mg/kg/day,at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0 mg/kg/day,at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20 mg/kg/day, atleast 25 mg/kg/day, at least 30 mg/kg/day, at least 35 mg/kg/day, atleast 40 mg/kg/day, at least 45 mg/kg/day, or at least 50 mg/kg/day. Inother aspects of this embodiment, an effective amount of a statindisclosed herein may be in the range of, e.g., about 0.001 mg/kg/day toabout 10 mg/kg/day, about 0.001 mg/kg/day to about 15 mg/kg/day, about0.001 mg/kg/day to about 20 mg/kg/day, about 0.001 mg/kg/day to about 25mg/kg/day, about 0.001 mg/kg/day to about 30 mg/kg/day, about 0.001mg/kg/day to about 35 mg/kg/day, about 0.001 mg/kg/day to about 40mg/kg/day, about 0.001 mg/kg/day to about 45 mg/kg/day, about 0.001mg/kg/day to about 50 mg/kg/day, about 0.001 mg/kg/day to about 75mg/kg/day, or about 0.001 mg/kg/day to about 100 mg/kg/day. In yet otheraspects of this embodiment, an effective amount of a statin disclosedherein may be in the range of, e.g., about 0.01 mg/kg/day to about 10mg/kg/day, about 0.01 mg/kg/day to about 15 mg/kg/day, about 0.01mg/kg/day to about 20 mg/kg/day, about 0.01 mg/kg/day to about 25mg/kg/day, about 0.01 mg/kg/day to about 30 mg/kg/day, about 0.01mg/kg/day to about 35 mg/kg/day, about 0.01 mg/kg/day to about 40mg/kg/day, about 0.01 mg/kg/day to about 45 mg/kg/day, about 0.01mg/kg/day to about 50 mg/kg/day, about 0.01 mg/kg/day to about 75mg/kg/day, or about 0.01 mg/kg/day to about 100 mg/kg/day. In stillother aspects of this embodiment, an effective amount of a statindisclosed herein may be in the range of, e.g., about 0.1 mg/kg/day toabout 10 mg/kg/day, about 0.1 mg/kg/day to about 15 mg/kg/day, about 0.1mg/kg/day to about 20 mg/kg/day, about 0.1 mg/kg/day to about 25mg/kg/day, about 0.1 mg/kg/day to about 30 mg/kg/day, about 0.1mg/kg/day to about 35 mg/kg/day, about 0.1 mg/kg/day to about 40mg/kg/day, about 0.1 mg/kg/day to about 45 mg/kg/day, about 0.1mg/kg/day to about 50 mg/kg/day, about 0.1 mg/kg/day to about 75mg/kg/day, or about 0.1 mg/kg/day to about 100 mg/kg/day.

In other aspects of this embodiment, an effective amount of artemesininand/or a derivative thereof disclosed herein may be in the range of,e.g., about 1 mg/kg/day to about 10 mg/kg/day, about 1 mg/kg/day toabout 15 mg/kg/day, about 1 mg/kg/day to about 20 mg/kg/day, about 1mg/kg/day to about 25 mg/kg/day, about 1 mg/kg/day to about 30mg/kg/day, about 1 mg/kg/day to about 35 mg/kg/day, about 1 mg/kg/day toabout 40 mg/kg/day, about 1 mg/kg/day to about 45 mg/kg/day, about 1mg/kg/day to about 50 mg/kg/day, about 1 mg/kg/day to about 75mg/kg/day, or about 1 mg/kg/day to about 100 mg/kg/day. In yet otheraspects of this embodiment, an effective amount of a statin disclosedherein may be in the range of, e.g., about 5 mg/kg/day to about 10mg/kg/day, about 5 mg/kg/day to about 15 mg/kg/day, about 5 mg/kg/day toabout 20 mg/kg/day, about 5 mg/kg/day to about 25 mg/kg/day, about 5mg/kg/day to about 30 mg/kg/day, about 5 mg/kg/day to about 35mg/kg/day, about 5 mg/kg/day to about 40 mg/kg/day, about 5 mg/kg/day toabout 45 mg/kg/day, about 5 mg/kg/day to about 50 mg/kg/day, about 5mg/kg/day to about 75 mg/kg/day, or about 5 mg/kg/day to about 100mg/kg/day.

In other aspects of this embodiment, a therapeutically effective amountof artemesinin and/or a derivative thereof disclosed herein generally isin the range of about 1 mg/day to about 3,000 mg/day. In aspects of thisembodiment, an effective amount of a statin disclosed herein may be,e.g., at least 50 mg/day, at least 100 mg/day, at least 150 mg/day, atleast 200 mg/day, at least 250 mg/day, at least 300 mg/day, at least 350mg/day, at least 400 mg/day, at least 450 mg/day, at least 500 mg/day,at least 550 mg/day, at least 600 mg/day, at least 650 mg/day, at least700 mg/day, at least 750 mg/day, at least 800 mg/day, at least 850mg/day, at least 900 mg/day, at least 950 mg/day, at least 1,000 mg/day,at least 1.50 mg/day, at least 1,100 mg/day, at least 1,150 mg/day, atleast 1,200 mg/day, at least 1,250 mg/day, at least 1,300 mg/day, atleast 1,350 mg/day, at least 1,400 mg/day, at least 1,450 mg/day, atleast 1,500 mg/day, at least 1,600 mg/day, at least 1,700 mg/day, atleast 1,800 mg/day, at least 1,900 mg/day, at least 2,000 mg/day, atleast 2,100 mg/day, at least 2,200 mg/day, at least 2,300 mg/day, atleast 2,400 mg/day, at least 2,500 mg/day, at least 2,600 mg/day, atleast 2,700 mg/day, at least 2,800 mg/day, at least 2,900 mg/day, or atleast 3,000 mg/day. In yet other aspects of this embodiment, aneffective amount of a statin disclosed herein may be between, e.g.,about 50 mg/day to about 1,000 mg/day, about 100 mg/day to about 1,000mg/day, about 150 mg/day to about 1,000 mg/day, about 200 mg/day toabout 1,000 mg/day, about 250 mg/day to about 1,000 mg/day, about 300mg/day to about 1,000 mg/day, about 350 mg/day to about 1,000 mg/day,about 400 mg/day to about 1,000 mg/day, about 450 mg/day to about 1,000mg/day, about 500 mg/day to about 1,000 mg/day, about 50 mg/day to about1,500 mg/day, about 100 mg/day to about 1,500 mg/day, about 150 mg/dayto about 1,500 mg/day, about 200 mg/day to about 1,500 mg/day, about 250mg/day to about 1,500 mg/day, about 300 mg/day to about 1,500 mg/day,about 350 mg/day to about 1,500 mg/day, about 400 mg/day to about 1,500mg/day, about 450 mg/day to about 1,500 mg/day, about 500 mg/day toabout 1,500 mg/day, about 1,000 mg/day to about 3,000 mg/day, about1,100 mg/day to about 3,000 mg/day, about 1,200 mg/day to about 3,000mg/day, about 1,3000 mg/day to about 3,000 mg/day, about 1,400 mg/day toabout 3,000 mg/day, about 1,500 mg/day to about 3,000 mg/day, about1,600 mg/day to about 3,000 mg/day, about 1,700 mg/day to about 3,000mg/day, about 1,800 mg/day to about 3,000 mg/day, about 1,900 mg/day toabout 3,000 mg/day, or about 2,000 mg/day to about 3,000 mg/day.

In other aspects of this embodiment, in conjunction with artemesininand/or a derivative thereof, a therapeutically effective amount of asecond, different cancer therapeutic is in the range of about 0.001mg/kg/day to about 100 mg/kg/day. In aspects of this embodiment, inconjunction with aretemesinin and/or a derivative thereof, atherapeutically effective amount of a second, different cancertherapeutic may be, e.g., at least 0.001 mg/kg/day, at least 0.01mg/kg/day, at least 0.1 mg/kg/day, at least 1.0 mg/kg/day, at least 5.0mg/kg/day, at least 10 mg/kg/day, at least 15 mg/kg/day, at least 20mg/kg/day, at least 25 mg/kg/day, at least 30 mg/kg/day, at least 35mg/kg/day, at least 40 mg/kg/day, at least 45 mg/kg/day, or at least 50mg/kg/day. In other aspects of this embodiment, in conjunction witharetemesinin and/or a derivative thereof, a therapeutically effectiveamount of a second, different cancer therapeutic may be in the range of,e.g., about 0.001 mg/kg/day to about 10 mg/kg/day, about 0.001 mg/kg/dayto about 15 mg/kg/day, about 0.001 mg/kg/day to about 20 mg/kg/day,about 0.001 mg/kg/day to about 25 mg/kg/day, about 0.001 mg/kg/day toabout 30 mg/kg/day, about 0.001 mg/kg/day to about 35 mg/kg/day, about0.001 mg/kg/day to about 40 mg/kg/day, about 0.001 mg/kg/day to about 45mg/kg/day, about 0.001 mg/kg/day to about 50 mg/kg/day, about 0.001mg/kg/day to about 75 mg/kg/day, or about 0.001 mg/kg/day to about 100mg/kg/day. In yet other aspects of this embodiment, in conjunction witharetemesinin and/or a derivative thereof, a therapeutically effectiveamount of a second, different cancer therapeutic may be in the range of,e.g., about 0.01 mg/kg/day to about 10 mg/kg/day, about 0.01 mg/kg/dayto about 15 mg/kg/day, about 0.01 mg/kg/day to about 20 mg/kg/day, about0.01 mg/kg/day to about 25 mg/kg/day, about 0.01 mg/kg/day to about 30mg/kg/day, about 0.01 mg/kg/day to about 35 mg/kg/day, about 0.01mg/kg/day to about 40 mg/kg/day, about 0.01 mg/kg/day to about 45mg/kg/day, about 0.01 mg/kg/day to about 50 mg/kg/day, about 0.01mg/kg/day to about 75 mg/kg/day, or about 0.01 mg/kg/day to about 100mg/kg/day. In still other aspects of this embodiment, in conjunctionwith aretemesinin and/or a derivative thereof, a therapeuticallyeffective amount of a second, different cancer therapeutic herein may bein the range of, e.g., about 0.1 mg/kg/day to about 10 mg/kg/day, about0.1 mg/kg/day to about 15 mg/kg/day, about 0.1 mg/kg/day to about 20mg/kg/day, about 0.1 mg/kg/day to about 25 mg/kg/day, about 0.1mg/kg/day to about 30 mg/kg/day, about 0.1 mg/kg/day to about 35mg/kg/day, about 0.1 mg/kg/day to about 40 mg/kg/day, about 0.1mg/kg/day to about 45 mg/kg/day, about 0.1 mg/kg/day to about 50mg/kg/day, about 0.1 mg/kg/day to about 75 mg/kg/day, or about 0.1mg/kg/day to about 100 mg/kg/day.

Dosing can be single dosage or cumulative (serial dosing), and can bereadily determined by one skilled in the art. For instance, reducing ormaintaining a cancer cell population and/or tumor cell size iin anindividual may comprise a one-time administration of an effective doseof a pharmaceutical composition disclosed herein. Alternatively,reducing or maintaining a cancer cell population and/or tumor cell sizeiin an individual may comprise multiple administrations of an effectivedose of a pharmaceutical composition carried out over a range of timeperiods, such as, e.g., once daily, twice daily, trice daily, once everyfew days, or once weekly. The timing of administration can vary fromindividual to individual, depending upon such factors as the severity ofan individual's symptoms. For example, an effective dose of apharmaceutical composition disclosed herein can be administered to anindividual once daily for an indefinite period of time, or until theindividual no longer requires therapy. A person of ordinary skill in theart will recognize that the condition of the individual can be monitoredthroughout the course of treatment and that the effective amount of apharmaceutical composition disclosed herein that is administered can beadjusted accordingly.

Various routes of administration can be useful for administering atherapeutic compound disclosed herein, according to a method forreducing and/or maintaining a cancer cell population and/or tumor cellsize in an individual. A pharmaceutical composition may be administeredto an individual by any of a variety of means depending, e.g., on thespecific therapeutic compound or composition used, or other compound tobe included in the composition, and the history, risk factors andsymptoms of the individual. As such, topical, enteral, oral,intravenous, subcutaneous, intranasal, rectal, vaginal, intramuscular orparenteral routes of administration may be suitable for reducing ormaintaining a cancer cell population and/or tumor cell size in anindividual as disclosed herein and such routes include both local andsystemic delivery of a therapeutic compound or composition disclosedherein. Compositions comprising either a single therapeutic compounddisclosed herein, or two or more therapeutic compounds disclosed hereinare intended for inhaled, topical, intranasal, oral, subcutaneous,sublingual, intravenous, rectal and/or vaginal use may be preparedaccording to any method known to the art for the manufacture ofpharmaceutical compositions. A pharmaceutical composition disclosedherein can be administered to an individual in a single formulation orin separate formulations, for combined, simultaneous or sequentialadministration.

Aspects of the present specification may also be described as follows:

1. A pharmaceutical composition comprising a cancer therapeutic and apharmaceutically acceptable lipid formulation.

2. The pharmaceutical formulation of embodiment 1, wherein the cancertherapeutic is Artemisnin.

3. The pharmaceutical formulation of embodiment 1, wherein the cancertherapeutic is a derivative of Artemesinin.

4. The pharmaceutical formulation of embodiment 3, wherein thederivative of Artemesinin is Artesunate, Artemether, Dihydroartemisinin,Artelinic acid, Artenimol and/or Artemotil.

5. The pharmaceutical composition of embodiment 1, wherein thecomposition includes a pharmaceutically acceptable solvent, apharmaceutically acceptable stabilizing agent, a pharmaceuticallyacceptable carrier and/or a pharmaceutically acceptable component.6. The pharmaceutical composition of any proceeding embodiment, whereinthe cancer therapeutic is capable of reducing the number of cancer cellsor tumor size in an individual suffering from a cancer by, at least 10%,at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, atleast 40%, at least 45%, at least 50%, at least 55%, at least 60%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90% or at least 95% as compared to a patient not receiving thesame treatment.7. The pharmaceutical composition of any proceeding embodiment, whereinthe cancer therapeutic is capable of reducing the number of cancer cellsor tumor size in an individual suffering from a cancer by, about 10% toabout 100%, about 20% to about 100%, about 30% to about 100%, about 40%to about 100%, about 50% to about 100%, about 60% to about 100%, about70% to about 100%, about 80% to about 100%, about 10% to about 90%,about 20% to about 90%, about 30% to about 90%, about 40% to about 90%,about 50% to about 90%, about 60% to about 90%, about 70% to about 90%,about 10% to about 80%, about 20% to about 80%, about 30% to about 80%,about 40% to about 80%, about 50% to about 80%, or about 60% to about80%, about 10% to about 70%, about 20% to about 70%, about 30% to about70%, about 40% to about 70%, or about 50% to about 70% as compared to apatient not receiving the same treatment.8. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is an alkylating agent.9. The pharmaceutical composition of embodiment 8, wherein thealkylating agent is Cisplatin, carboplatin, mechlorethamine,cyclophosphamide, chlorambucil, ifosfamide and/or oxaliplatin.10. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is an anti-metabolite.11. The pharmaceutical composition of embodiment 10, wherein theanti-metabolite is azathioprine and/or mercaptopurine.12. The pharmaceutical composition of embodiment 10, wherein theanti-metabolite is a synthetic, semisynthetic or derivative of ananti-metabolite.13. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is a terpenoid.14. The pharmaceutical composition of embodiment 13, wherein theterpenoid is a vinca alkaloid and/or a taxane.15. The pharmaceutical composition of embodiment 14, wherein the vincaalkaloid is Vincristine, Vinblastine, Vinorelbine and/or Vindesine.16. The pharmaceutical composition of embodiment 14, wherein the taxaneis Taxol, Pacllitaxel and/or Docetaxel.17. The pharmaceutical composition of embodiment 14, wherein the taxaneis a synthetic, semisynthetic or derivative of a taxane.18. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is a topoisomerase.19. The pharmaceutical composition of embodiment 18, wherein thetopoisomerase is a type I topoisomerase.20. The pharmaceutical composition of embodiment 19, wherein the type 1topoisomerase is camptothecins.21. The pharmaceutical composition of embodiment 20, wherein thecampotothecins is irinotecan and/or topotecan.22. The pharmaceutical composition of embodiment 18, wherein thetopoisomerase is a type II topoisomerase.23. The pharmaceutical composition of embodiment 22, wherein the type IItopoisomerase is amsacrine, etoposide, etoposide phosphate and/orteniposide.24. The pharmaceutical composition of any of embodiments 18-23, whereinthe topoisomerase is a synthetic, semisynthetic and/or derivative.25. The pharmaceutical composition of embodiment 24, wherein thederivative is epipodophyllotoxins.26. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is a cytotoxic antibiotic.27. The pharmaceutical composition of embodiment 26, wherein thecytotoxic antibiotic is actinomycin, anthracyclines, doxorubicin,daunorubicin, valrubicin, idarubicin, epirubicin, bleomycin, plicamycinand/or mitomycin.28. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is a hormone.29. The pharmaceutical composition of embodiment 28, wherein the hormoneis a lutenizing hormone releasing hormone agonist.30. The pharmaceutical composition of embodiment 28, wherein the hormoneis leuprolidine, goserelin, triptorelin, histrelin, bicalutamide,flutamide and/or nilutamide.31. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is an antibody.32. The pharmaceutical composition of embodiment 31, wherein theantibody is Abciximab, Adalimumab, Alemtuzumab, Atlizumab, Basiliximab,Belimumab, Bevacizumab, Bretuximab vedotin, Canakinumab, Cetuximab,Ceertolizumab pegol, Daclizumab, Denosumab, Eculizumab, Efalizumab,Gemtuzumab, Golimumab, Golimumab, Ibritumomab tiuxetan, Infliximab,Ipilimumab, Muromonab-CD3, Natalizumab, Ofatumumab, Omalizumab,Palivizumab, Panitumuab, Ranibizumab, Rituximab, Tocilizumab,Tositumomab and/or Trastuzumab.33. The pharmaceutical composition of embodiment 3, wherein thederivative is a butyrate ester of dihydroartemesinin.34. The pharmaceutical composition of any of the preceding embodiments,wherein the cancer therapeutic has a half-life of one hour.35. The pharmaceutical composition of any of the preceding embodiments,wherein the dosing of the cancer therapeutic is daily.36. The pharmaceutical composition of any of the preceding embodiments,wherein the cancer therapeutic has a half-life of 2 hours, 3 hours, 4hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours,12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 2 days, 3 days, 4days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, onemonth, two months, three months and/or four months.37. The pharmaceutical composition of any of the preceding embodiments,wherein the cancer therapeutic is administered to an individual for aperiod of time followed by a separate period of time.38. The pharmaceutical composition of any of the preceding embodiments,wherein the cancer therapeutic is administered for a first period and asecond period following the first period, with administration stoppedduring the second period, followed by a third period whereadministration of the therapeutic compound is started and then a fourthperiod following the third period where administration is stopped.39. The pharmaceutical composition of any of the preceding embodiments,wherein the cancer therapeutic is administered for 1 day, 2 days, 3days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days,12 days, 13 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks,8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months,or more. In a further embodiment, a period of during whichadministration is stopped is for 1 day, 2 days, 3 days, 4 days, 5 days,6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6 months, 7 months, 8months, 9 months, 10 months, 11 months and/or 12 months.40. The pharmaceutical composition of any of the preceding embodiments,wherein a first cancer therapeutic s administered to an individual andat a later date, a second cancer therapeutic is administered to the sameindividual.41. The pharmaceutical composition of any of the preceding embodiments,wherein the first therapeutic compound is artemesinin or a derivativethereof and the second therapeutic compound is a different derivative ofartemesinin.42. The pharmaceutical composition of any of the preceding embodiments,wherein the first therapeutic compound is artemesinin or a derivativethereof and the second therapeutic compound is a cancer therapeutic thatis not artemesinin or a derivative thereof.43. The pharmaceutical composition of any of the preceding embodiments,wherein a first therapeutic compound is administered to an individual atthe same time as a second therapeutic compound is administered to theindividual.44. The pharmaceutical composition of any of the preceding embodiments,wherein the first therapeutic compound is a artemesinin or derivativethereof and the second therapeutic compound is a different derivative ofartemesinin.45. The pharmaceutical composition of any of the preceding embodiments,wherein the first therapeutic compound is artemesinin or a derivativethereof and the second therapeutic compound is a cancer therapeutic thatis not artemesinin or a derivative thereof.46. The pharmaceutical composition of any of the preceding embodiments,wherein the pharmaceutical composition is a liquid, a sold and/or asemi-solid.47. The pharmaceutical composition of embodiment 46, wherein, thepharmaceutical composition is provided to an individual in a capsule,tablet, pill, lozenge, powder and/or granule.48. The pharmaceutical composition of embodiment 46, wherein thepharmaceutical composition is inhaled.49. The pharmaceutical composition of embodiment 1, wherein thepharmaceutical composition is formulated in an oil-in-water emulsion.50. The pharmaceutical composition of embodiment 49, wherein the oil isa vegetable oil, an animal fat and/or a mineral oil.51. The pharmaceutical composition of embodiment 1, wherein thepharmaceutical composition is released in a controlled release profileover time.52. The pharmaceutical composition of embodiment 1, wherein thepharmaceutical composition is provided in an extended releasetherapeutic compound delivery form.53. The pharmaceutical composition of embodiment 1, wherein thepharmaceutical composition is provided in a sustained releasetherapeutic compound deliver form.54. The pharmaceutical composition of embodiment 53, wherein thesustained release therapeutic compound delivery platform releases atherapeutic compound with substantially zero order release kinetics overa period of about 7 days after administration, about 15 days afteradministration, about 30 days after administration, about 45 days afteradministration, about 60 days after administration, about 75 days afteradministration and/or about 90 days after administration.55. The pharmaceutical composition of embodiment 53, wherein thesustained release therapeutic compound delivery platform releases atherapeutic compound with substantially zero order release kinetics overa period of at least 7 days after administration, at least 15 days afteradministration, at least 30 days after administration, at least 45 daysafter administration, at least 60 days after administration, at least 75days after administration, or at least 90 days after administration.56. The pharmaceutical composition of embodiment 53, wherein thesustained release therapeutic compound delivery platform releases atherapeutic compound with substantially first order release kineticsover a period of about 7 days after administration, about 15 days afteradministration, about 30 days after administration, about 45 days afteradministration, about 60 days after administration, about 75 days afteradministration, or about 90 days after administration.57. The pharmaceutical composition of embodiment 53, wherein thesustained release therapeutic compound delivery platform releases atherapeutic compound with substantially first order release kineticsover a period of at least 7 days after administration, at least 15 daysafter administration, at least 30 days after administration, at least 45days after administration, at least 60 days after administration, atleast 75 days after administration, or at least 90 days afteradministration.58. The pharmaceutical composition of embodiment 53, wherein atherapeutic compound delivery platform releases a therapeutic compoundwith substantially zero order release kinetics over a period of about 1day after administration, about 2 days after administration, about 3days after administration, about 4 days after administration, about 5days after administration, or about 6 days after administration.59. The pharmaceutical composition of embodiment 53, wherein atherapeutic compound delivery platform releases a therapeutic compoundwith substantially zero order release kinetics over a period of, e.g.,at most 1 day after administration, at most 2 days after administration,at most 3 days after administration, at most 4 days afteradministration, at most 5 days after administration, or at most 6 daysafter administration.60. The pharmaceutical composition of embodiment 53, wherein atherapeutic compound delivery platform releases a therapeutic compounddisclosed herein with substantially first order release kinetics over aperiod of about 1 day after administration, about 2 days afteradministration, about 3 days after administration, about 4 days afteradministration, about 5 days after administration, or about 6 days afteradministration.61. The pharmaceutical composition of embodiment 53, wherein atherapeutic compound delivery platform releases a therapeutic compounddisclosed herein with substantially first order release kinetics over aperiod of at most 1 day after administration, at most 2 days afteradministration, at most 3 days after administration, at most 4 daysafter administration, at most 5 days after administration, or at most 6days after administration.62. The pharmaceutical composition of any preceeding embodiment, whereina therapeutic compound has a log P value indicating that the compound isat least 50% soluble in an organic solvent, at least 60% soluble in anorganic solvent, at least 70% soluble in an organic solvent, at least80% soluble in an organic solvent, or at least 90% soluble in an organicsolvent.63. The pharmaceutical composition of any preceeding embodiment, whereina therapeutic compound has a log P value indicating that the compound isbetween, e.g., about 50% to about 100% soluble in an organic solvent,about 60% to about 100% soluble in an organic solvent, about 70% toabout 100% soluble in an organic solvent, about 80% to about 100%soluble in an organic solvent, or about 90% to about 100% soluble in anorganic solvent.64. The pharmaceutical composition of any preceeding embodiment, whereina therapeutic compound has a log P value of, e.g., more than 1.1, morethan 1.2, more than 1.4, more than 1.6, more than 1.8, more than 2.0,more than 2.2, more than 2.4, more than 2.6, more than 2.8, more than3.0, more than 3.2, more than 3.4, or more than 3.6.65. The pharmaceutical composition of any preceeding embodiment, whereina therapeutic compound has a log P value in the range of, e.g., between1.8 and 4.0, between 2.0 and 4.0, between 2.1 and 4.0, between 2.2 and4.0, or between 2.3 and 4.0, between 2.4 and 4.0, between 2.5 and 4.0,between 2.6 and 4.0, or between 2.8 and 4.0. 66. The pharmaceuticalcomposition of any preceeding embodiment, wherein a therapeutic compoundhas a log P value in the range of, e.g., between 3.0 and 4.0, or between3.1 and 4.0, between 3.2 and 4.0, between 3.3 and 4.0, between 3.4 and4.0, between 3.5 and 4.0, or between 3.6 and 4.0.67. The pharmaceutical composition of any preceeding embodiment,wherein, a therapeutic compound has a log P value in the range of, e.g.,between 2.0 and 2.5, between 2.0 and 2.7, between 2.0 and 3.0, orbetween 2.2 and 2.5.68. The pharmaceutical composition of any preceeding embodiment, whereina therapeutic compound has a polar surface area of, e.g., less than 8.0nm², less than 7.0 nm², less than 6.0 nm², less than 5.0 nm², less than4.0 nm², or less than 3.0 nm².69. The pharmaceutical composition of any preceeding embodiment, whereina therapeutic compound has a polar surface area in the range of, e.g.,between 3.0 nm² and 6.5 nm², between 3.0 nm² and 6.0 nm², between 3.0nm² and 5.5 nm², between 3.0 nm² and 5.0 nm², between 3.0 nm² and 4.5nm², between 3.5 nm² and 6.5 nm², between 3.5 nm² and 6.0 nm², between3.5 nm² and 5.5 nm², between 3.5 nm² and 5.0 nm², between 3.5 nm² and4.5 nm², between 4.0 nm² and 6.5 nm², between 4.0 nm² and 6.0 nm²,between 4.0 nm² and 5.5 nm², or between 4.0 nm² and 5.0 nm², between 4.0nm² and 4.5 nm², or between 4.5 nm² and 5.5 nm².70. The pharmaceutical composition of any preceeding embodiment, whereina therapeutic compound has a polar surface area in the range of, e.g.,between 2.0 nm² and 6.5 nm², between 2.0 nm² and 6.0 nm², between 2.0nm² and 5.5 nm², between 2.0 nm² and 5.0 nm², between 2.0 nm² and 4.5nm², between 2.5 nm² and 6.5 nm², between 2.5 nm² and 6.0 nm², between2.5 nm² and 5.5 nm², between 2.5 nm² and 5.0 nm², or between 2.5 nm² and4.5 nm².71. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is an ester.72. The pharmaceutical composition of embodiment 5, wherein the solventis in an amount sufficient to dissolve a cancer therapeutic.73. The pharmaceutical composition of embodiment 72, wherein thepharmaceutical comprises a solvent in an amount of less than about 90%(v/v), less than about 80% (v/v), less than about 70% (v/v), less thanabout 65% (v/v), less than about 60% (v/v), less than about 55% (v/v),less than about 50% (v/v), less than about 45% (v/v), less than about40% (v/v), less than about 35% (v/v), less than about 30% (v/v), lessthan about 25% (v/v), less than about 20% (v/v), less than about 15%(v/v), less than about 10% (v/v), less than about 5% (v/v), or less thanabout 1% (v/v).74. The pharmaceutical composition of embodiment 72, wherein thepharmaceutical composition comprises a solvent in an amount in a rangeof, e.g., about 1% (v/v) to 90% (v/v), about 1% (v/v) to 70% (v/v),about 1% (v/v) to 60% (v/v), about 1% (v/v) to 50% (v/v), about 1% (v/v)to 40% (v/v), about 1% (v/v) to 30% (v/v), about 1% (v/v) to 20% (v/v),about 1% (v/v) to 10% (v/v), about 2% (v/v) to 50% (v/v), about 2% (v/v)to 40% (v/v), about 2% (v/v) to 30% (v/v), about 2% (v/v) to 20% (v/v),about 2% (v/v) to 10% (v/v), about 4% (v/v) to 50% (v/v), about 4% (v/v)to 40% (v/v), about 4% (v/v) to 30% (v/v), about 4% (v/v) to 20% (v/v),about 4% (v/v) to 10% (v/v), about 6% (v/v) to 50% (v/v), about 6% (v/v)to 40% (v/v), about 6% (v/v) to 30% (v/v), about 6% (v/v) to 20% (v/v),about 6% (v/v) to 10% (v/v), about 8% (v/v) to 50% (v/v), about 8% (v/v)to 40% (v/v), about 8% (v/v) to 30% (v/v), about 8% (v/v) to 20% (v/v),about 8% (v/v) to 15% (v/v), or about 8% (v/v) to 12% (v/v).75. The pharmaceutical composition of embodiment 5, wherein the solventcomprises a pharmaceutically acceptable alcohol.76. The pharmaceutical composition of embodiment 75, wherein the alcoholis a C₂₋₄ alcohol, a C₁₋₄ alcohol, a C₁₋₅ alcohol, a C₁₋₇ alcohol, aC₁₋₁₀ alcohol, a C₁₋₁₅ alcohol, or a C₁₋₂₀ alcohol.77. The pharmaceutical composition of embodiment 75, wherein the alcoholis a primary alcohol, a secondary alcohol, or a tertiary alcohol.78. The pharmaceutical composition of embodiment 75, wherein the alcoholis an acyclic alcohol, a monohydric alcohol, a polyhydric alcohol (alsoknown as a polyol or sugar alcohol), an unsaturated aliphatic alcohol,an alicyclic alcohol, or a combination thereof.79. The pharmaceutical composition of embodiment 75, wherein the alcoholis an unsaturated aliphatic alcohol.80. The pharmaceutical composition of embodiment 75, wherein theunsaturated aliphatic alcohol is prop-2-ene-1-ol,3,7-dimethylocta-2,6-dien-1-ol, and prop-2-in-1-ol.81. The pharmaceutical composition of embodiment 75, wherein an alcoholis an alicyclic alcohol.82. The pharmaceutical composition of embodiment 75, wherein thealicyclic alcohol is cyclohexane-1,2,3,4,5,6-hexol and2-(2-propyl)-5-methyl-cyclohexane-1-ol. 83. The pharmaceuticalcomposition of embodiment 5, wherein a solvent is an ester ofpharmaceutically-acceptable alcohol and an acid.84. The pharmaceutical composition of embodiment 83 wherein an ester ofa pharmaceutically-acceptable acid is acetic acid, butaric acid, andformic acid.85. The pharmaceutical composition of embodiment 83, wherein the esterof an alcohol and an acid are methyl acetate, methyl buterate, methylformate, ethyl acetate, ethyl buterate, ethyl formate, propyl acetate,propyl buterate, propyl formate, butyl acetate, butyl buterate, butylformate, isobutyl acetate, isobutyl buterate, isobutyl formate, pentylacetate, pentyl buterate, pentyl formate, and 1-hexadecyl acetate,1-hexadecyl buterate or 1-hexadecyl formate.86. The pharmaceutical composition of embodiment 5, wherein the solventis a pharmaceutically-acceptable glycol either.87. The pharmaceutical composition of embodiment 86, wherein the glycolether is diethylene glycol monomethyl ether(2-(2-methoxyethoxy)ethanol), diethylene glycol monoethyl ether(2-(2-ethoxyethoxy)ethanol), diethylene glycol monopropyl ether(2-(2-propoxyethoxy)ethanol), diethylene glycol monoisopropyl ether(2-(2-isopropoxyethoxy)ethanol), and diethylene glycol mono-n-butylether (2-(2-butoxyethoxy)ethanol).88. The pharmaceutical composition of embodiment 5, wherein thecomposition comprises one or more lipids.89. The pharmaceutical composition of embodiment 88, wherein the lipidis a fatty acids, glycerolipids, diglycerides, and triglycerides),phospholipids, sphingolipids, sterol lipids, prenol lipids,saccharolipids, and/or polyketides.90. The pharmaceutical composition of embodiment 88, wherein the lipidis an oil, an oil-based liquid, a fat, a fatty acid, a partiallyhydrolyzed fatty acid, a wax, a fatty acid ester, a fatty acid salt, afatty alcohol, a glyceride (mono-, di- or tri-glyceride), aphospholipids, a glycol ester, a sucrose ester, a glycerol oleatederivative, a medium chain triglyceride and or a partially hydrolyzedtriglyceride.91. The pharmaceutical composition of embodiment 88, wherein the lipidis Capryllic acid (8:0), pelargonic acid (9:0), Capric acid (10:0),Undecylic acid (11:0), Lauric acid (12:0), Tridecylic acid (13:0),Myristic acid (14:0), Myristoleic acid (14:1), Pentadecyclic acid(15:0), Palmitic acid (16:0), Palmitoleic acid (16:1), Sapienic acid(16:1), Margaric acid (17:0), Stearic acid (18:0), Oleic acid (18:1),Elaidic acid (18:1), Vaccenic acid (18:1), Linoleic acid (18:2),Linoelaidic acid (18:2), α-Linolenic acid (18:3), γ-Linolenic acid(18:3), Stearidonic acid (18:4), Nonadecylic acid (19:0), Arachidic acid(20:0), Eicosenoic acid (20:1), Dihomo-γ-linolenic acid (20:3), Meadacid (20:3), Arachidonic acid (20:4), Eicosapentaenoic acid (20:5),Heneicosylic acid (21:0), Behenic acid (22:0), Erucic acid (22:1),Docosahexaenoic acid (22:6), Tricosylic acid (23:0), Lignoceric acid(24:0), Nervonic acid (24:1), Pentacosylic acid (25:0), Cerotic acid(26:0), Heptacosylic acid (27:0), Montanic acid (28:0), Nonacosylic acid(29:0), Melissic acid (30:0), Henatriacontylic acid (31:0), Lacceroicacid (32:0), Psyllic acid (33:0), Geddic acid (34:0), Ceroplastic acid(35:0), and/or Hexatriacontylic acid (36:0).92. The pharmaceutical composition of embodiment 88, wherein the lipidis a pharmaceutically-acceptable saturated or unsaturated fatty acid.93. The pharmaceutical composition of embodiment 92, wherein thesaturated or unsaturated fatty acid comprises at least 8, at least 10,at least 12, at least 14, at least 16, at least 18, at least 20, atleast 22, at least 24, at least 26, at least 28, or at least 30 carbonatoms, 94. The pharmaceutical composition of embodiment 92, wherein thesaturated or unsaturated fatty acid comprises between 4 and 24 carbonatoms, between 6 and 24 carbon atoms, between 8 and 24 carbon atoms,between 10 and 24 carbon atoms, between 12 and 24 carbon atoms, between14 and 24 carbon atoms, or between 16 and 24 carbon atoms, between 4 and22 carbon atoms, between 6 and 22 carbon atoms, between 8 and 22 carbonatoms, between 10 and 22 carbon atoms, between 12 and 22 carbon atoms,between 14 and 22 carbon atoms, or between 16 and 22 carbon atoms,between 4 and 20 carbon atoms, between 6 and 20 carbon atoms, between 8and 20 carbon atoms, between 10 and 20 carbon atoms, between 12 and 20carbon atoms, between 14 and 20 carbon atoms, or between 16 and 20carbon atoms.95. The pharmaceutical composition of embodiment 92, wherein theunsaturated fatty acid has 1 or more, 2 or more, 3 or more, 4 or more, 5or more, or 6 or more double bonds.96. The pharmaceutical composition of any proceeding embodiment, whereinthe concentration of a therapeutic compound is at least 0.00001 mg/mL,at least 0.0001 mg/mL, at least 0.001 mg/mL, at least 0.01 mg/mL, atleast 0.1 mg/mL, at least 1 mg/mL, at least 10 mg/mL, at least 25 mg/mL,at least 50 mg/mL, at least 100 mg/mL, at least 200 mg/mL, at least 500mg/mL, at least 700 mg/mL, at least 1,000 mg/mL, or at least 1,200mg/mL.97. The pharmaceutical composition of any proceeding embodiment, whereinthe concentration of a therapeutic compound is at most 1,000 mg/mL, atmost 1,100 mg/mL, at most 1,200 mg/mL, at most 1,300 mg/mL, at most1,400 mg/mL, at most 1,500 mg/mL, at most 2,000 mg/mL, at most 2,000mg/mL, or at most 3,000 mg/mL.98. The pharmaceutical composition of any proceeding embodiment, whereinthe concentration of a therapeutic compound is about 0.00001 mg/mL toabout 3,000 mg/mL, about 0.0001 mg/mL to about 3,000 mg/mL, about 0.01mg/mL to about 3,000 mg/mL, about 0.1 mg/mL to about 3,000 mg/mL, about1 mg/mL to about 3,000 mg/mL, about 250 mg/mL to about 3,000 mg/mL,about 500 mg/mL to about 3,000 mg/mL, about 750 mg/mL to about 3,000mg/mL, about 1,000 mg/mL to about 3,000 mg/mL, about 100 mg/mL to about2,000 mg/mL, about 250 mg/mL to about 2,000 mg/mL, about 500 mg/mL toabout 2,000 mg/mL, about 750 mg/mL to about 2,000 mg/mL, about 1,000mg/mL to about 2,000 mg/mL, about 100 mg/mL to about 1,500 mg/mL, about250 mg/mL to about 1,500 mg/mL, about 500 mg/mL to about 1,500 mg/mL,about 750 mg/mL to about 1,500 mg/mL, about 1,000 mg/mL to about 1,500mg/mL, about 100 mg/mL to about 1,200 mg/mL, about 250 mg/mL to about1,200 mg/mL, about 500 mg/mL to about 1,200 mg/mL, about 750 mg/mL toabout 1,200 mg/mL, about 1,000 mg/mL to about 1,200 mg/mL, about 100mg/mL to about 1,000 mg/mL, about 250 mg/mL to about 1,000 mg/mL, about500 mg/mL to about 1,000 mg/mL, about 750 mg/mL to about 1,000 mg/mL,about 100 mg/mL to about 750 mg/mL, about 250 mg/mL to about 750 mg/mL,about 500 mg/mL to about 750 mg/mL, about 100 mg/mL to about 500 mg/mL,about 250 mg/mL to about 500 mg/mL, about 0.00001 mg/mL to about 0.0001mg/mL, about 0.00001 mg/mL to about 0.001 mg/mL, about 0.00001 mg/mL toabout 0.01 mg/mL, about 0.00001 mg/mL to about 0.1 mg/mL, about 0.00001mg/mL to about 1 mg/mL, about 0.001 mg/mL to about 0.01 mg/mL, about0.001 mg/mL to about 0.1 mg/mL, about 0.001 mg/mL to about 1 mg/mL,about 0.001 mg/mL to about 10 mg/mL, or about 0.001 mg/mL to about 100mg/mL.99. The pharmaceutical composition of any proceeding embodiment, whereinthe ratio of solution:adjuvant is at least 5:1, at least 4:1, at least3:1, at least 2:1, at least 0:1, at least 1:1, at least 1:2, at least1:3, at least 1:4, at least 1:5, at least 1:6, at least 1:7, at least1:8, at least 1:9, at least 1:10, at least 1:15, at least 1:20, or atleast 1:25.100. The pharmaceutical composition of any proceeding embodiment,wherein the ratio of solution:adjuvant is about 5:1 to about 1:25, about4:1 to about 1:25, about 3:1 to about 1:25, about 2:1 to about 1:25,about 0:1 to about 1:25, about 1:1 to about 1:25, about 1:2 to about1:25, about 1:3 to about 1:25, about 1:4 to about 1:25, about 1:5 toabout 1:25, about 5:1 to about 1:20, about 4:1 to about 1:20, about 3:1to about 1:20, about 2:1 to about 1:20, about 0:1 to about 1:20, about1:1 to about 1:20, about 1:2 to about 1:20, about 1:3 to about 1:20,about 1:4 to about 1:20, about 1:5 to about 1:20, about 5:1 to about1:15, about 4:1 to about 1:15, about 3:1 to about 1:15, about 0:1 toabout 1:15, about 2:1 to about 1:15, about 1:1 to about 1:15, about 1:2to about 1:15, about 1:3 to about 1:15, about 1:4 to about 1:15, about1:5 to about 1:15, about 5:1 to about 1:12, about 4:1 to about 1:12,about 3:1 to about 1:12, about 2:1 to about 1:12, about 0:1 to about1:12, about 1:1 to about 1:12, about 1:2 to about 1:12, about 1:3 toabout 1:12, about 1:4 to about 1:12, about 1:5 to about 1:12, about 1:6to about 1:12, about 1:7 to about 1:12, about 1:8 to about 1:12, about5:1 to about 1:10, about 4:1 to about 1:10, about 3:1 to about 1:10,about 2:1 to about 1:10, about 0:1 to about 1:10, about 1:1 to about1:10, about 1:2 to about 1:10, about 1:3 to about 1:10, about 1:4 toabout 1:10, about 1:5 to about 1:10, about 1:6 to about 1:10, about 1:7to about 1:10, or about 1:8 to about 1:10.101. The pharmaceutical composition of any proceeding embodiment,wherein the ratio of fat:fat, is at least 5:1, at least 4:1, at least3:1, at least 2:1, at least 0:1, at least 1:1, at least 1.1:1, at least1.2:1, at least 1.3:1, at least 1.4:1, at least 1.5:1, at least 1.6:1,at least 1.7:1, at least 1.8:1, at least 1.9:1, at least 1:2, at least1:3, at least 1:4, at least 1:5, at least 1:6, at least 1:7, at least1:8, at least 1:9, at least 1:10, at least 1:15, at least 1:20, or atleast 1:25.102. The pharmaceutical composition of any proceeding embodiment,wherein the ratio of fat:fat may be in a range of about 5:1 to about1:25, about 4:1 to about 1:25, about 3:1 to about 1:25, about 2:1 toabout 1:25, about 0:1 to about 1:25, about 1:1 to about 1:25, about 1:2to about 1:25, about 1:3 to about 1:25, about 1:4 to about 1:25, about1:5 to about 1:25, about 5:1 to about 1:20, about 4:1 to about 1:20,about 3:1 to about 1:20, about 2:1 to about 1:20, about 0:1 to about1:20, about 1:1 to about 1:20, about 1:2 to about 1:20, about 1:3 toabout 1:20, about 1:4 to about 1:20, about 1:5 to about 1:20, about 5:1to about 1:15, about 4:1 to about 1:15, about 3:1 to about 1:15, about0:1 to about 1:15, about 2:1 to about 1:15, about 1:1 to about 1:15,about 1:2 to about 1:15, about 1:3 to about 1:15, about 1:4 to about1:15, about 1:5 to about 1:15, about 5:1 to about 1:12, about 4:1 toabout 1:12, about 3:1 to about 1:12, about 2:1 to about 1:12, about 0:1to about 1:12, about 1:1 to about 1:12, about 1:2 to about 1:12, about1:3 to about 1:12, about 1:4 to about 1:12, about 1:5 to about 1:12,about 1:6 to about 1:12, about 1:7 to about 1:12, about 1:8 to about1:12, about 5:1 to about 1:10, about 4:1 to about 1:10, about 3:1 toabout 1:10, about 2:1 to about 1:10, about 0:1 to about 1:10, about 1:1to about 1:10, about 1:2 to about 1:10, about 1:3 to about 1:10, about1:4 to about 1:10, about 1:5 to about 1:10, about 1:6 to about 1:10,about 1:7 to about 1:10, or about 1:8 to about 1:10.103. The pharmaceutical composition of any proceeding embodiment,wherein the ratio of fat:fat, in a pharmaceutical composition containingartemesinin or a derivate thereof, is at least 5:1, at least 4:1, atleast 3:1, at least 2:1, at least 0:1, at least 1:1, at least 1.1:1, atleast 1.2:1, at least 1.3:1, at least 1.4:1, at least 1.5:1, at least1.6:1, at least 1.7:1, at least 1.8:1, at least 1.9:1, at least 1:2, atleast 1:3, at least 1:4, at least 1:5, at least 1:6, at least 1:7, atleast 1:8, at least 1:9, at least 1:10, at least 1:15, at least 1:20, orat least 1:25.104. The pharmaceutical composition of any proceeding embodiment,wherein the ratio of fat:fat, in a pharmaceutical composition containingartemesinin ora derivate thereof, is in a range of about 5:1 to about1:25, about 4:1 to about 1:25, about 3:1 to about 1:25, about 2:1 toabout 1:25, about 0:1 to about 1:25, about 1:1 to about 1:25, about 1:2to about 1:25, about 1:3 to about 1:25, about 1:4 to about 1:25, about1:5 to about 1:25, about 5:1 to about 1:20, about 4:1 to about 1:20,about 3:1 to about 1:20, about 2:1 to about 1:20, about 0:1 to about1:20, about 1:1 to about 1:20, about 1:2 to about 1:20, about 1:3 toabout 1:20, about 1:4 to about 1:20, about 1:5 to about 1:20, about 5:1to about 1:15, about 4:1 to about 1:15, about 3:1 to about 1:15, about0:1 to about 1:15, about 2:1 to about 1:15, about 1:1 to about 1:15,about 1:2 to about 1:15, about 1:3 to about 1:15, about 1:4 to about1:15, about 1:5 to about 1:15, about 5:1 to about 1:12, about 4:1 toabout 1:12, about 3:1 to about 1:12, about 2:1 to about 1:12, about 0:1to about 1:12, about 1:1 to about 1:12, about 1:2 to about 1:12, about1:3 to about 1:12, about 1:4 to about 1:12, about 1:5 to about 1:12,about 1:6 to about 1:12, about 1:7 to about 1:12, about 1:8 to about1:12, about 5:1 to about 1:10, about 4:1 to about 1:10, about 3:1 toabout 1:10, about 2:1 to about 1:10, about 0:1 to about 1:10, about 1:1to about 1:10, about 1:2 to about 1:10, about 1:3 to about 1:10, about1:4 to about 1:10, about 1:5 to about 1:10, about 1:6 to about 1:10,about 1:7 to about 1:10, or about 1:8 to about 1:10.105. The pharmaceutical composition of embodiment 88, wherein a cancertherapeutic is formulated in a one fat.106. The pharmaceutical composition of embodiment 88, whereinartemesinin or a derivative thereof is formulated in one fat.107. The pharmaceutical composition of embodiment 88, wherein a cancertherapeutic is formulated in two fats.108. The pharmaceutical composition of embodiment 88, whereinartemesinin or a derivative thereof is formulated in two fats.109. The pharmaceutical composition of embodiment 88, wherein a cancertherapeutic is formulated in three fats, four fats, five fats, six fatsor seven or more fats.110. The pharmaceutical composition of embodiment 88, whereinartemesinin or a derivative thereof is formulated in three fats, fourfats, five fats, six fats or seven or more fats.111. The pharmaceutical composition of embodiment 88, wherein a cancertherapeutic is formulated in a fat that is a liquid.112. The pharmaceutical composition of embodiment 88, wherein a cancertherapeutic is formulated in at fat that is a solid.113. The pharmaceutical composition of embodiment 88, wherein a cancertherapeutic is formulated in a two or more fats that are liquids.114. The pharmaceutical composition of embodiment 88, wherein a cancertherapeutic is formulated in two or more fats that are solids.115. The pharmaceutical composition of embodiment 88, wherein a cancertherapeutic is formulated in two or more fats, wherein at least one fatis a solid and at least one fat is a liquid.116. The pharmaceutical composition of any of embodiments 111-115,wherein the cancer therapeutic is artemesinin and/or a derivativetherof.117. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is at least 0.00001mg/mL, at least 0.0001 mg/mL, at least 0.001 mg/mL, at least 0.01 mg/mL,at least 0.1 mg/mL, at least 1 mg/mL, at least 10 mg/mL, at least 25mg/mL, at least 50 mg/mL, at least 100 mg/mL, at least 200 mg/mL, atleast 500 mg/mL, at least 700 mg/mL, at least 1,000 mg/mL, or at least1,200 mg/mL.118. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is at most 1,000mg/mL, at most 1,100 mg/mL, at most 1,200 mg/mL, at most 1,300 mg/mL, atmost 1,400 mg/mL, at most 1,500 mg/mL, at most 2,000 mg/mL, at most2,000 mg/mL, or at most 3,000 mg/mL.119. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is about 0.00001 mg/mLto about 3,000 mg/mL, about 0.0001 mg/mL to about 3,000 mg/mL, about0.01 mg/mL to about 3,000 mg/mL, about 0.1 mg/mL to about 3,000 mg/mL,about 1 mg/mL to about 3,000 mg/mL, about 250 mg/mL to about 3,000mg/mL, about 500 mg/mL to about 3,000 mg/mL, about 750 mg/mL to about3,000 mg/mL, about 1,000 mg/mL to about 3,000 mg/mL, about 100 mg/mL toabout 2,000 mg/mL, about 250 mg/mL to about 2,000 mg/mL, about 500 mg/mLto about 2,000 mg/mL, about 750 mg/mL to about 2,000 mg/mL, about 1,000mg/mL to about 2,000 mg/mL, about 100 mg/mL to about 1,500 mg/mL, about250 mg/mL to about 1,500 mg/mL, about 500 mg/mL to about 1,500 mg/mL,about 750 mg/mL to about 1,500 mg/mL, about 1,000 mg/mL to about 1,500mg/mL, about 100 mg/mL to about 1,200 mg/mL, about 250 mg/mL to about1,200 mg/mL, about 500 mg/mL to about 1,200 mg/mL, about 750 mg/mL toabout 1,200 mg/mL, about 1,000 mg/mL to about 1,200 mg/mL, about 100mg/mL to about 1,000 mg/mL, about 250 mg/mL to about 1,000 mg/mL, about500 mg/mL to about 1,000 mg/mL, about 750 mg/mL to about 1,000 mg/mL,about 100 mg/mL to about 750 mg/mL, about 250 mg/mL to about 750 mg/mL,about 500 mg/mL to about 750 mg/mL, about 100 mg/mL to about 500 mg/mL,about 250 mg/mL to about 500 mg/mL, about 0.00001 mg/mL to about 0.0001mg/mL, about 0.00001 mg/mL to about 0.001 mg/mL, about 0.00001 mg/mL toabout 0.01 mg/mL, about 0.00001 mg/mL to about 0.1 mg/mL, about 0.00001mg/mL to about 1 mg/mL, about 0.001 mg/mL to about 0.01 mg/mL, about0.001 mg/mL to about 0.1 mg/mL, about 0.001 mg/mL to about 1 mg/mL,about 0.001 mg/mL to about 10 mg/mL, or about 0.001 mg/mL to about 100mg/mL.120. The pharmaceutical composition of any of embodiments 1-4, whereinthe composition is a liquid, semi-solid or a solid formulation.121. The pharmaceutical composition of any of embodiments 1-4 and 88,wherein the pharmaceutical composition comprises tributyrin and G43122. The pharmaceutical composition of any of embodiments 1-4, whereinan artemesinin or a derivative thereof is linked to a estrogen receptormodulator.123. The pharmaceutical composition of embodiment 122, wherein theestrogen receptor modulator is a selective estrogen receptor modulator.124. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is a stilbenoid.125. The pharmaceutical composition of embodiment 124, wherein thestilbenoid is Resveratrol, Piceatannol, Pinosylvin, Pterostilbene,Alpha-Viniferin, Ampelopsin A, Ampelopsin E, Diptoindonesin C,Diptoindonesin F, Epsilon-Vinferin, Flexuosol A, Gnetin H, HemsleyanolD, Hopeaphenol, Trans-Diptoindonesin B, Astringin, Piceid andDiptoindonesin A.126. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is an isoflavone.127. The pharmaceutical composition of embodiment 124, wherein theisoflavone is Daidzein or Genistein.128. The pharmaceutical composition of embodiment 1, wherein the cancertherapeutic is an isoflavondiol.129. The pharmaceutical composition of embodiment 124, wherein theisoflavondiol is Daidzein or Genistein.130. The pharmaceutical composition of any of embodiments 124-129,wherein the cancer therapeutic is administered with an Artemesinin.131. The pharmaceutical composition of embodiment 130, wherein theArtemesinin is a derivative of Artemesinin.132. The pharmaceutical composition of embodiment 131, wherein thederivative is Artesunate, Artemether, Dihydroartemisinin, Artelinicacid, Artenimol and/or Artemotil.133. The pharmaceutical composition of any of embodiments 124-129,wherein the stilbenoid, isoflavone and/or isoflavondiol is a synthetic,semisynthetic or derivative.134. A pharmaceutical composition comprising one or more cancertherapeutics.135. The pharmaceutical formulation of embodiment 134, wherein a cancertherapeutic is selected from an alkylating agent, an anti-metabolite, aplant alkaloid, a terpenoid, a topoisomerase inhibitor, a cytotoxicantibiotics, a statin, an anti-diabetic drug, a PPAR-y, a PPAR-J3, aPPAR-a, an antibiotic, an antihelminthic, an anti-malaria drug, avitamin and/or a food additive.136. The pharmaceutical formulation of embodiment 135, wherein thealkylating agent is carboplatin, chlorambucil, cisplatin,cyclophosphamide, ifosfamide, oxaliplatin and/or mechlorethamine.137. The pharmaceutical formulation of embodiment 135, wherein theantimetabolite is azathioprine and/or mercaptopurine.138. The pharmaceutical formulation of embodiment 135, wherein the plantalkaloid is a vinca alkaloid, a podophyllotoxin and/or a taxane.139. The pharmaceutical formulation of embodiment 135, wherein the vincaalkaloid is vincristine, vinblastine, vinorelbine and/or vindesine.140. The pharmaceutical formulation of embodiment 135, wherein thepodophyllotoxin is etoposide and/or teniposide.141. The pharmaceutical formulation of embodiment 135, wherein thetaxane is docetaxel and/or ortataxel.142. The pharmaceutical formulation of embodiment 135, wherein thetopoisomerase is a type Itopoisomerase inhibitor or a type IItopoisomerase inhibitor.143. The pharmaceutical formulation of embodiment 135, wherein the typeI topoisomerase inhibitor is a camptothecin.144. The pharmaceutical formulation of embodiment 135, wherein thecamptothecin is exatecan, irinotecan, lurtotecan, topotecan, BNP 1350,CKD 602, DB 67 (AR67) and/or ST 1481.145. The pharmaceutical formulation of embodiment 135, wherein the typeII topoisomerase inhibitor is epipodophyllotoxin.146. The pharmaceutical formulation of embodiment 135, wherein theepipodophyllotoxin is, without limitation, amsacrine, etoposid,etoposide phosphate and/orteniposide.147. The pharmaceutical formulation of embodiment 135, wherein thecytotoxic antibiotic is an actinomycin, an anthracenedione, ananthracycline, thalidomide, dichloroacetic acid, nicotinic acid,2-deoxyglucose and/or chlofazimine.148. The pharmaceutical formulation of embodiment 135, wherein theactinomycin is actinomycin D, bacitracin, colistin (polymyxin E) and/orpolymyxin B.149. The pharmaceutical formulation of embodiment 135, wherein theantracenedione is mitoxantrone and/or pixantrone.150. The pharmaceutical formulation of embodiment 135, wherein theanthracycline is bleomycin, doxorubicin (Adriamycin), daunorubicin(daunomycin), epirubicin, idarubicin, mitomycin, plicamycin and/orvalrubicin.151. The pharmaceutical formulation of embodiment 135, wherein thestatin is atorvastatin, fluvastin, lovastatin, pitavastatin,pravastatin, rosuvastatin and/or simvastatin.152. The pharmaceutical formulation of embodiment 135, wherein thetreatment of diabetes is a biguanide, a thiazolidinedione, asecretagogue, an alpha-glucosidase inhibitor and/or a peptide analog.153. The pharmaceutical formulation of embodiment 135, wherein thebiguanide is metformin, phenformin and/or buformin.154. The pharmaceutical formulation of embodiment 135, wherein thethiazolidinedione is rosiglitazone, pioglitazone and/or trogliazone.155. The pharmaceutical formulation of embodiment 135, wherein thesecretagogue is a sulfonylurea, a nonsulfonylurea and/or a meglitinide.156. The pharmaceutical formulation of embodiment 135, wherein thesulfonylurea is tolbutamide, acetohexamide, tolazamide, chlorpropamide,glipzide, glyburide, glimepiride, gliclazide, glycopyramide and/orgliquidone.157. The pharmaceutical formulation of embodiment 135, wherein themeglitinide is repaglinide and/or nateglinide.158. The pharmaceutical formulation of embodiment 135, wherein thealpha-glucosidase inhibitor is miglitol, acarbose and/or voglibose.159. The pharmaceutical formulation of embodiment 135, wherein thepeptide analog is an injectable incretin mimetic, an injectableglucagon-like peptide analog and/or agonist, a gastric inhibitorypeptide analog, a dipeptidyl peptidase-4 inhibitor and/or an injectableAmylin analogue.160. The pharmaceutical formulation of embodiment 135, wherein theglucagon-like peptide analog and/or agonist is exenatide, liraglutideand/or taspoglutide.161. The pharmaceutical formulation of embodiment 135, wherein thedipeptidyl peptidase-4 inhibitor is vildagliptin, sitagliptin,saxagliptin, linagliptin, allogliptin and/or septagliptin.162. The pharmaceutical formulation of embodiment 135, wherein theinjectable Amylin analogue is pramlintide.163. The pharmaceutical formulation of embodiment 135, wherein thecancer therapeutic is cinnamon and/or thiamine.164. The pharmaceutical formulation of embodiment 135, wherein thePeroxisome proliferator-activated receptor gamma is rosigliazone,troglitazone, pioglitazone, netoglitazone, rivoglitazone and/orciglitazone.165. The pharmaceutical formulation of embodiment 135, wherein thePPAR-r3 agonist is endurobol and/or GW0742.166. The pharmaceutical formulation of embodiment 135, wherein theantibiotic is soniazid, rifampicin, pyrazinamide and/or ethambutol.167. The pharmaceutical formulation of embodiment 135, wherein theantihelminthic is abamectin, an aminoacetonitriles, a benzimadazole,diethylcaramazine, ivermectin, levamisole, niclosamide, anoctadepsipeptides, phosphoric acid (metrifonate), praziquantel, aspiroindoles, suramin and/or pyrantel pamoate.168. The pharmaceutical formulation of embodiment 135, wherein theaminoacetonitrile is monepantel.169. The pharmaceutical formulation of embodiment 135, wherein thebenzimidazole is albendazole, fenbendazole, a flubendazole,thiabendazole and triclabendazole.170. The pharmaceutical formulation of embodiment 135, wherein theflubendazole is mebendazole.171. The pharmaceutical formulation of embodiment 135, wherein theoctadepsipeptide is emodepside.172. The pharmaceutical formulation of embodiment 135, wherein thespiroindole is dequantel.173. The pharmaceutical formulation of embodiment 135, wherein theanti-malarial therapeutic is amodiaquine, an artemisinin, atovaquone,chloroquine, clindamycin, doxycycline, halofantrine, mefloquine,primaquine, proguanil, pyrimethamine, a quinine and related agent,rufigallol, and/or a sulphonamide.174. The pharmaceutical formulation of embodiment 135, wherein theartemisinin is artemether, artesunate and/or dihydroartemisinin.175. The pharmaceutical formulation of embodiment 135, wherein thequinine and related agent is quinimax and/or quinidine.176. The pharmaceutical formulation of embodiment 135, wherein thesulfonamide is sulfadoxine and/or sulfamethoxypyridazine.177. The pharmaceutical formulation of embodiment 135, wherein the foodadditive and/or vitamin is tributerin, vitamin C, vitamin 812, vitaminD, resveratrol and/or coenzymeQ12.178. The pharmaceutical formulation of embodiment 135, wherein theglucose intake inhibitor is a GLUT-1 receptor inhibitor.179. The pharmaceutical formulation of embodiment 135, wherein the lipidintake inhibitor is an LDL receptor inhibitor, an SR-81 inhibitor, anSR-82 inhibitor and/or a SR-83/CD36 (thrombospondi n) receptorinhibitor.180. The pharmaceutical formulation of any of embodiments 136-179,wherein an individual is administered one or more of the cancertherapeutics.181. The pharmaceutical composition of any of the proceedingembodiments, wherein a pharmaceutical composition includes apharmaceutically acceptable solvent, a pharmaceutically acceptablestabilizing agent, a pharmaceutically acceptable carrier and/or apharmaceutically acceptable component.182. The pharmaceutical composition of any proceeding embodiment,wherein a cancer therapeutic is capable of reducing the number of cancercells or tumor size in an individual suffering from a cancer by, atleast 10%, at least 15%, at least 20%, at least 25%, at least 30%, atleast 35%, at least 40%, at least 45%, at least 50%, at least 55%, atleast 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90% or at least 95% as compared to a patient notreceiving the same treatment.183. The pharmaceutical composition of any proceeding embodiment,wherein a cancer therapeutic is capable of reducing the number of cancercells or tumor size in an individual suffering from a cancer by, about10% to about 100%, about 20% to about 100%, about 30% to about 100%,about 40% to about 100%, about 50% to about 100%, about 60% to about100%, about 70% to about 100%, about 80% to about 100%, about 10% toabout 90%, about 20% to about 90%, about 30% to about 90%, about 40% toabout 90%, about 50% to about 90%, about 60% to about 90%, about 70% toabout 90%, about 10% to about 80%, about 20% to about 80%, about 30% toabout 80%, about 40% to about 80%, about 50% to about 80%, or about 60%to about 80%, about 10% to about 70%, about 20% to about 70%, about 30%to about 70%, about 40% to 70%, about 50% to 70% as compared to apatient not receiving the same treatment.184. The pharmaceutical composition of any of the preceding embodiments,wherein a cancer therapeutic has a half-lie of one hour.185. The pharmaceutical composition of any of the preceding embodiments,wherein the dosing of a cancer therapeutic is daily.186. The pharmaceutical composition of any of the preceding embodiments,wherein a cancer therapeutic has a half-life of 2 hours, 3 hours, 4hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours,12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 2 days, 3 days, 4days, 5 days, 6 days, 7 days, 1 week, 2 weeks, 3 weeks, 4 weeks, onemonth, two months, three months and/or four months.187. The pharmaceutical composition of any of the preceding embodiments,wherein a cancer therapeutic is administered to an individual for aperiod of time followed by a separate period of time.188. The pharmaceutical composition of any of the preceding embodiments,wherein a cancer therapeutic is administered for a first period and asecond period following the first period, with administration stoppedduring the second period, followed by a third period whereadministration of the cancer therapeutic is started and then a fourthperiod following the third period where administration is stopped.189. The pharmaceutical composition of any of the preceding embodiments,wherein a cancer therapeutic is administered for 1 day, 2 days, 3 days,4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12days, 13 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 4 months, 5 months, 6months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months,or more.190. The pharmaceutical composition of any of the preceding embodiments,wherein a first cancer therapeutic s administered to an individual andat a later date, a second cancer therapeutic is administered to the sameindividual191. The pharmaceutical composition of any of the preceding embodiments,wherein a first cancer therapeutic is administered to an individual atthe same time as a second cancer therapeutic is administered to theindividual.192. The pharmaceutical composition of any of the preceding embodiments,wherein the pharmaceutical composition is a liquid, a sold and/or asemi-solid.193. The pharmaceutical composition of embodiment 192, wherein, thepharmaceutical composition is provided to an individual in a capsule,tablet, pill, lozenge, powder and/or granule.194. The pharmaceutical composition of embodiment 192, wherein thepharmaceutical composition is inhaled.195. The pharmaceutical composition of embodiment 134, wherein thepharmaceutical composition is formulated in an oil-in-water emulsion.196. The pharmaceutical composition of embodiment 195, wherein the oilis a vegetable oil, an animal fat and/or a mineral oil.197. The pharmaceutical composition of any of embodiments 134-180,wherein the pharmaceutical composition is released in a controlledrelease profile over time.198. The pharmaceutical composition of any of embodiments 134-180,wherein the pharmaceutical composition is provided in an extendedrelease cancer therapeutic delivery form.199. The pharmaceutical composition of any of embodiments 134-180,wherein the pharmaceutical composition is provided in a sustainedrelease cancer therapeutic deliver form.200. The pharmaceutical composition of embodiment 199, wherein thesustained release cancer therapeutic delivery platform releases a cancertherapeutic with substantially zero order release kinetics over a periodof about 7 days after administration, about 15 days afteradministration, about 30 days after administration, about 45 days afteradministration, about 60 days after administration, about 75 days afteradministration and/or about 90 days after administration.201. The pharmaceutical composition of embodiment 199, wherein thesustained release cancer therapeutic delivery platform releases a cancertherapeutic with substantially zero order release kinetics over a periodof at least 7 days after administration, at least 15 days afteradministration, at least 30 days after administration, at least 45 daysafter administration, at least 60 days after administration, at least 75days after administration, or at least 90 days after administration.202. The pharmaceutical composition of embodiment 199, wherein thesustained release cancer therapeutic delivery platform releases a cancertherapeutic with substantially first order release kinetics over aperiod of about 7 days after administration, about 15 days afteradministration, about 30 days after administration, about 45 days afteradministration, about 60 days after administration, about 75 days afteradministration, or about 90 days after administration.203. The pharmaceutical composition of embodiment 199, wherein thesustained release cancer therapeutic delivery platform releases a cancertherapeutic with substantially first order release kinetics over aperiod of at least 7 days after administration, at least 15 days afteradministration, at least 30 days after administration, at least 45 daysafter administration, at least 60 days after administration, at least 75days after administration, or at least 90 days after administration.204. The pharmaceutical composition of embodiment 199, wherein a cancertherapeutic delivery platform releases a cancer therapeutic withsubstantially zero order release kinetics over a period of about 1 dayafter administration, about 2 days after administration, about 3 daysafter administration, about 4 days after administration, about 5 daysafter administration, or about 6 days after administration.205. The pharmaceutical composition of embodiment 199, wherein a cancertherapeutic delivery platform releases a cancer therapeutic withsubstantially zero order release kinetics over a period of, e.g., atmost 1 day after administration, at most 2 days after administration, atmost 3 days after administration, at most 4 days after administration,at most 5 days after administration, or at most 6 days afteradministration.206. The pharmaceutical composition of embodiment 199, wherein a cancertherapeutic delivery platform releases a cancer therapeutic disclosedherein with substantially first order release kinetics over a period ofabout 1 day after administration, about 2 days after administration,about 3 days after administration, about 4 days after administration,about 5 days after administration, or about 6 days after administration.207. The pharmaceutical composition of embodiment 199, wherein a cancertherapeutic delivery platform releases a cancer therapeutic disclosedherein with substantially first order release kinetics over a period ofat most 1 day after administration, at most 2 days after administration,at most 3 days after administration, at most 4 days afteradministration, at most 5 days after administration, or at most 6 daysafter administration.208. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is at least 0.00001mg/ml, at least 0.0001 mg/ml, at least 0.001 mg/ml, at least 0.01 mg/ml,at least 0.1 mg/ml, at least 1 mg/ml, at least 10 mg/ml, at least 25mg/ml, at least 50 mg/ml, at least 100 mg/ml, at least 200 mg/ml, atleast 500 mg/ml, at least 700 mg/ml, at least 1,000 mg/ml, or at least1,200 mg/ml.209. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is at most 1,000mg/ml, at most 1,100 mg/ml, at most 1,200 mg/ml, at most 1,300 mg/ml, atmost 1,400 mg/ml, at most 1,500 mg/ml, at most 2,000 mg/ml, at most2,000 mg/ml, or at most 3,000 mg/ml.210. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is about 0.00001 mg/mlto about 3,000 mg/ml, about 0.0001 mg/ml to about 3,000 mg/ml, about0.01 mg/ml to about 3,000 mg/ml, about 0.1 mg/ml to about 3,000 mg/ml,about 1 mg/ml to about 3,000 mg/ml, about 250 mg/ml to about 3,000mg/ml, about 500 mg/ml to about 3,000 mg/ml, about 750 mg/ml to about3,000 mg/ml, about 1,000 mg/ml to about 3,000 mg/ml, about 100 mg/ml toabout 2,000 mg/ml, about 250 mg/ml to about 2,000 mg/ml, about 500 mg/mlto about 2,000 mg/ml, about 750 mg/ml to about 2,000 mg/ml, about 1,000mg/ml to about 2,000 mg/ml, about 100 mg/ml to about 1,500 mg/ml, about250 mg/ml to about 1,500 mg/ml, about 500 mg/ml to about 1,500 mg/ml,about 750 mg/ml to about 1,500 mg/ml, about 1,000 mg/ml to about 1,500mg/ml, about 100 mg/ml to about 1,200 mg/ml, about 250 mg/ml to about1,200 mg/ml, about 500 mg/ml to about 1,200 mg/ml, about 750 mg/ml toabout 1,200 mg/ml, about 1,000 mg/ml to about 1,200 mg/ml, about 100mg/ml to about 1,000 mg/ml, about 250 mg/ml to about 1,000 mg/ml, about500 mg/ml to about 1,000 mg/ml, about 750 mg/ml to about 1,000 mg/ml,about 100 mg/ml to about 750 mg/ml, about 250 mg/ml to about 750 mg/ml,about 500 mg/ml to about 750 mg/ml, about 100 mg/ml to about 500 mg/ml,about 250 mg/ml to about 500 mg/ml, about 0.00001 mg/ml to about 0.0001mg/ml, about 0.00001 mg/ml to about 0.001 mg/ml, about 0.00001 mg/ml toabout 0.01 mg/ml, about 0.00001 mg/ml to about 0.1 mg/ml, about 0.00001mg/ml to about 1 mg/ml, about 0.001 mg/ml to about 0.01 mg/ml, about0.001 mg/ml to about 0.1 mg/ml, about 0.001 mg/ml to about 1 mg/ml,about 0.001 mg/ml to about 10 mg/ml, or about 0.001 mg/ml to about 100mg/ml.211. The pharmaceutical composition of any of embodiments 134-180,wherein a cancer therapeutic is formulated in one fat.212. The pharmaceutical composition of any of embodiments 134-180,wherein a cancer therapeutic is formulated in two fats.213. The pharmaceutical composition of any of embodiments 134-180,wherein a cancer therapeutic is formulated in three fats, four fats,five fats, six fats or seven or more fats.214. The pharmaceutical composition of any of embodiments 134-180,wherein a cancer therapeutic is formulated in a fat that is a liquid.215. The pharmaceutical composition of any of embodiments 134-180,wherein a cancer therapeutic is formulated in at fat that is a solid.216. The pharmaceutical composition of any of embodiments 134-180,wherein a cancer therapeutic is formulated in two or more fats that areliquids.217. The pharmaceutical composition of any of embodiments 134-180,wherein a cancer therapeutic is formulated in two or more fats that aresolids.218. The pharmaceutical composition of any of embodiments 134-180,wherein a cancer therapeutic is formulated in two or more fats, whereinat least one fat is a solid and at least one fat is a liquid.219. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is at least 0.00001mg/ml, at least 0.0001 mg/ml, at least 0.001 mg/ml, at least 0.01 mg/ml,at least 0.1 mg/ml, at least 1 mg/ml, at least 10 mg/ml, at least 25mg/ml, at least 50 mg/ml, at least 100 mg/ml, at least 200 mg/ml, atleast 500 mg/ml, at least 700 mg/ml, at least 1,000 mg/ml, or at least1,200 mg/ml.220. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is at most 1,000mg/ml, at most 1,100 mg/ml, at most 1,200 mg/ml, at most 1,300 mg/ml, atmost 1,400 mg/ml, at most 1,500 mg/ml, at most 2,000 mg/ml, at most2,000 mg/ml, or at most 3,000 mg/ml.221. The pharmaceutical composition of any proceeding embodiment,wherein the concentration of a cancer therapeutic is about 0.00001 mg/mlto about 3,000 mg/ml, about 0.0001 mg/ml to about 3,000 mg/ml, about0.01 mg/ml to about 3,000 mg/ml, about 0.1 mg/ml to about 3,000 mg/ml,about 1 mg/ml to about 3,000 mg/ml, about 250 mg/ml to about 3,000mg/ml, about 500 mg/ml to about 3,000 mg/ml, about 750 mg/ml to about3,000 mg/ml, about 1,000 mg/ml to about 3,000 mg/ml, about 100 mg/ml toabout 2,000 mg/ml, about 250 mg/ml to about 2,000 mg/ml, about 500 mg/mlto about 2,000 mg/ml, about 750 mg/ml to about 2,000 mg/ml, about 1,000mg/ml to about 2,000 mg/ml, about 100 mg/ml to about 1,500 mg/ml, about250 mg/ml to about 1,500 mg/ml, about 500 mg/ml to about 1,500 mg/ml,about 750 mg/ml to about 1,500 mg/ml, about 1,000 mg/ml to about 1,500mg/ml, about 100 mg/ml to about 1,200 mg/ml, about 250 mg/ml to about1,200 mg/ml, about 500 mg/ml to about 1,200 mg/ml, about 750 mg/ml toabout 1,200 mg/ml, about 1,000 mg/ml to about 1,200 mg/ml, about 100mg/ml to about 1,000 mg/ml, about 250 mg/ml to about 1,000 mg/ml, about500 mg/ml to about 1,000 mg/ml, about 750 mg/ml to about 1,000 mg/ml,about 100 mg/ml to about 750 mg/ml, about 250 mg/ml to about 750 mg/ml,about 500 mg/ml to about 750 mg/ml, about 100 mg/ml to about 500 mg/ml,about 250 mg/ml to about 500 mg/ml, about 0.00001 mg/ml to about 0.0001mg/ml, about 0.00001 mg/ml to about 0.001 mg/ml, about 0.00001 mg/ml toabout 0.01 mg/ml, about 0.00001 mg/ml to about 0.1 mg/ml, about 0.00001mg/ml to about 1 mg/ml, about 0.001 mg/ml to about 0.01 mg/ml, about0.001 mg/ml to about 0.1 mg/ml, about 0.001 mg/ml to about 1 mg/ml,about 0.001 mg/ml to about 10 mg/ml, or about 0.001 mg/ml to about 100mg/ml.222. The pharmaceutical composition of any of embodiments 134-180,wherein the composition is a liquid, semi-solid or a solid formulation223. The pharmaceutical composition of any of embodiments 134-180,wherein the therapeutic results in a cancer cell not being able touptake sufficient quantities of glucose or other energy source resultingin the cell entering apoptosis and eventually dying.224. The pharmaceutical composition of any of embodiments 134-180,wherein the cancer therapeutic results in a cell not being able touptake sufficient quantities of a lipid, other fat and/or cholesterol,preventing the cancer cell from dividing and forming a progeny cancercell.

EXAMPLES Example 1

A patient comprising a 49 year old woman was diagnosed by her physicianwith advanced metastatic breast cancer. The metastatic breast cancerconsisted of tumors, including several found in both lungs. Thephysician prescribed a standard set of cancer therapeutics in an attemptto reduce or maintain the tumors. The patient did not tolerate thecancer therapeutics that were administered that consisted of Taxol andcapecitabine. The physician placed the patient on a paliative careregime and provided the patient with several doses of the aromataseinhibitor, letrazole. Following this treatment, the patient wasadministered a CAT scan, which revealed that her tumors wereprogressing, including one tumor in a lung that had grown by 50% inthree months. The patient was next administered a treatment consistingof artemether at a dose of 40 mg OD, presented in a lipid filled capsulecomprising tributyrin and G43. A CAT scan given to the patient severalmonths after administration of artemether found that all tumor growthhad stopped and the breast cancer did not progress in the patient duringthe period of artemether administration.

Example 2

A patient comprising a 50 year old woman was diagnosed by her physicianwith extensive metastaic breast cancer. The patient presented withtumors in brain liver and lungs. The patient also presented withsymptoms that included shortness of breath and a persistent cough. Thepatient informed the physician that she would not take part in astandard chemotherapy treatment protocol. The physician informed thepatient that she would only live for about three months survival. Thepatient was instead administered artemether at a dose of 40 mg OD,presented as a lipid filled capsule comprising tributyrin and G43. As aresult of the treatment, the symptoms the patient suffered from,including, shortness of breath and a persistent cough diminished overthe weeks following treatment with arthemether. The patient continues tosurvive, six months following the initial diagnosis.

Example 3

A patient comprising a 53 year old male was diagnosed with prostatecancer by his physician with several tumors in the prostate. Thephysician prescribed a hormone therapeutic formulated in a lipidformulation comprising tributyrin and G43. The patent was administeredthe therapeutic over a six month period, with a reduction in the size ofthe tumors. After several more months of treatment, the cancer wasdetermined to be in remission

Example 4

A patient comprising a 41 year old male was diagnosed with pancreaticcancer by his physician which had metastasized into the brain and liver.The physician prescribed chemotherapy, comprising a mixture of cancertherapeutics, including Gemzar, Tarceva and Avastin formulated in alipid formulation given as a liquid intravenously. The progression ofthe cancer slowed over time and several of the tumors were reduced insize. The patient who was given a three month life span lived for anadditional four years following initiation of treatment.

Example 5

A patient comprising a 37 year old female was diagnosed with acutemyeloid leukemia by her physician which had metastasized. The physicianprescribed chemotherapy, comprising a 40 mg OD of arthemether formulatedin a lipid formulation comprising tributyrin and G43. The progression ofthe cancer slowed over time. The patient continues to live and theirhealth is improving.

Example 6

A patient comprising a 71 year old woman was diagnosed by her physicianwith advanced metastatic breast cancer. The metastatic breast cancerconsisted of tumors, including several found in both lungs. Thephysician prescribed a standard set of cancer therapeutics in an attemptto reduce or maintain the tumors. The patient did not tolerate thecancer therapeutics that were administered that consisted of Taxol andcapecitabine. The physician placed the patient on a paliative careregime and provided the patient with several doses of the aromataseinhibitor, letrazole. Following this treatment, the patient wasadministered a CAT scan, which revealed that her tumors wereprogressing, including one tumor in a lung that had grown by 50% inthree months. The patient was next administered a treatment consistingof artemether at a dose of 40 mg OD, presented in a lipid filled capsulecomprising tributyrin and G43. A CAT scan given to the patient severalmonths after administration of artemether found that all tumor growthhad stopped and the breast cancer did not progress in the patient duringthe period of artemether administration.

Example 7

A patient comprising a 70 year old female was diagnosed with primaryperitoneal cancer by her physician with several tumors in her peritoneumthat included small tumors attached to her large intestine. The femalewas on chemotherapy and did not see either a reduction in her CancerAntigen 125 (“CA”) test or in the size or number of tumors. The femalebegan taking a combination of Metformin, Lipitor and Mebendazolepurchased from a pharmacy. The patient was administered the therapeuticcombination over a six month period, and during that time period,experienced a reduction in the size of the tumors. After several moremonths of treatment, the cancer was determined to be in remission.

Example 8

A patient comprising a 45 year old male was diagnosed with pancreaticcancer by his physician, which had metastasized into his brain andliver. The physician prescribed chemotherapy, comprising a mixture ofcancer therapeutics, including Gemzar, Tarceva and Avastin formulated ina lipid formulation given as a liquid intravenously. The progression ofthe cancer slowed over time and several of the tumors were reduced insize but the patient became progressively sicker. The chemotherapy wassupplemented with Arthemether, Simvastin, Metformin, Mebendazole andTributyrin. Following initiation of the treatment with these four drugs,the patient, began to become physically stronger.

Example 9

To assess the effect of Artesunate in combination with several othertherapeutics, MCF-7 cells were treated with different concentrations ofthese therapeutic compounds either once or through repeated dosing. Thepercentage of survival was calculated based on the LDH contents ofcells.

Protocol Followed:

Day −1: Seeding Cells in Wells of Plate

1. 100 ul of cells suspension (3×10⁴ cells l/m) were added to each well(3000 cells/well), with a total of 5 plates were seeded.

2. Plates were left at room temperature in the hood for 1 hour beforebeing placed in the incubator.

3. Some wells were left with no cells as background control.

Day 0: Treatment

50 ul of each therapeutic treatment was added to wells alreadycontaining 100 ul of the cell suspension at the doses indicated in thetemplate below for Sodium Butyrate, through similar concentrations wereused for Resveratrol, Daidzein and Equol:

Artesunate 1000 500 250 125 62.5 1000 500 250 125 62.5 ng/ml ng/ml ng/mlng/ml ng/ml ø ng/ml ng/ml ng/ml ng/ml ng/ml ø Sodium 4 mM Butyrate 2 mM1 mM 0.5 mM 0.25 mM 0.125 mM ø Cells in Cells in Vehic. Vehic. Cells inCM Cells in Vehicle Cells in MMC VehiclePreparation of Artesunate for Therapeutic Treatment

-   -   Using an analytical balance, Artesunate was weighed straight        into a 1.5 ml screw cap tube.    -   The appropriate volume of 100% Ethanol was added to Artesunate        to obtain a concentration of 10 mg/ml.    -   This was further diluted in 100% Ethanol to 1 mg/ml (1:10).    -   4 ug/ml was obtained by diluting 1 mg/ml (1:250) in complete        medium. Further double decreasing dilutions were carried out in        complete medium containing 0.4% Ethanol.        Preparation of Sodium Butyrate Dilutions for Therapeutic        Treatment    -   Using an analytical balance, Sodium Butyrate was weighed        straight into a 15 ml falcon tube.    -   The appropriate volume of complete medium was added to Sodium        Butyrate to obtain a concentration of 100 mM.    -   This was further diluted in complete medium to 16 mM (1:6.25).        Further double decreasing dilutions were carried out in complete        medium.        Preparation of Resveratrol Dilutions for Therapeutic Treatment    -   Using an analytical balance, Sodium Butyrate was weighed        straight into a 15 ml falcon tube.    -   The appropriate volume of complete medium was added to Sodium        Butyrate to obtain a concentration of 100 mM.    -   This was further diluted in complete medium to 16 mM (1:6.25).        Further double decreasing dilutions were carried out in complete        medium.        Preparation of Daidzein Dilutions for Therapeutic Treatment    -   Using an analytical balance, Sodium Butyrate was weighed        straight into a 15 ml falcon tube.    -   The appropriate volume of complete medium was added to Sodium        Butyrate to obtain a concentration of 100 mM.    -   This was further diluted in complete medium to 16 mM (1:6.25).        Further double decreasing dilutions were carried out in complete        medium.        Preparation of Equol Dilutions for Therapeutic Treatment    -   Using an analytical balance, Sodium Butyrate was weighed        straight into a 15 ml falcon tube.    -   The appropriate volume of complete medium was added to Sodium        Butyrate to obtain a concentration of 100 mM.    -   This was further diluted in complete medium to 16 mM (1:6.25).        Further double decreasing dilutions were carried out in complete        medium.        Preparation of Controls    -   2 mg of MMC were resuspended in 4 ml of sterile water to obtain        a stock at 0.5 mg/ml. A second dilution of MMC was carried out        by diluting 0.5 mg/ml in complete medium to 0.1 mg/ml (1:5).    -   Complete medium was prepared at 0.4% Ethanol        4. Once the treatments were ready, 50 ul/well of Artesunate was        added to the plates. Next, 50 ul of Sodium Butyrate,        Resveratrol, Daidzein or Equol were added to the wells already        containing 100 ul of cells suspension plus 50 ul of Artesunate.        5. 50 ul of complete medium at 0.4% Ethanol and 50 ul of just        complete medium were added to the corresponding control wells        already containing either 100 ul of cells (positive control) or        just 100 ul of complete medium (background control)        6. 100 ul of MMC at 100 ug/ml was added to the corresponding        wells already containing 100 ul of cells in complete medium as a        negative control and finally, plates were placed in the        incubator.        Day 1: Re-Dosing and LDH-24 h        7. 24 h after treatment of cells with a the aforementioned        therapeutics, two of the plates were re-dosed with the same        treatments described above, while another two plates were left        incubating as they were and the remaining plate was used to        measure the percent of survival by LDH through the following        method:    -   Media was removed from the wells by using a multichannel        pipette.    -   Wells were washed with 200 ul/well of PBS previously warmed at        37° C.    -   100 ul of Titron 1× in PBS previously warmed at 37° C. were        added to the wells. Subsequently, the plate was placed at 37° C.        in the dark for 45 min.    -   50 ul from each well was transferred to a non sterile 96-well        plate.    -   50 ul of LDH substrate were added to each well of the non        sterile plate already containing 50 ul/well of lysed cells and        the plates were then incubating at room temperature in the dark        for 30 min.    -   50 ul of Stop solution was added to each well and then the plate        was read at 492 nm.        Day 2: Re-Dosing, LDH-48 h and LDH-Re-Dosing at 24 h        8. After 48 h of cells treatment, one of the 2 plates that had        been re-dosed after 24 h was re-dosed again (treatments were        prepared as described above for re-dosing). One of the 2 plates        that had been treated just once will remain as it was in the        incubator. The remaining 2 plates were used to measure the % of        survival by LDH after 48 h of single treatment and after        re-dosing at 24 h (LDH assay was performed as described above).        Day 3: LDH-72 h and LDH-Re-Dosing at 24 h and at 48 h        After 72 h of cells treatment, there were just 2 plates left in        the incubator. They were used to measure the of survival by LDH        after 72 h of single treatment and after re-dosing at 24 h and        48 h (LDH assay was performed as described above).

In FIGS. 1 and 2, the results are provided for samples assessed 72 hoursafter wells containing MCF-7 cells (or no cells in a control) wereadministered either a single or a multiple dose of Artesunate and/orSodium Butyrate. As seen in both figures, Artesunate and Sodium Butyrateindividually decreased the survival of MCF-7 cells dosed once ormultiple times with one or the other therapeutic treatment. WhenArtesunate and Sodium Butyrate were administered in combination to theMCF-7 cells, the percent of cells that survived was less than whenArtesunate and Sodium Butyrate were administered individually. (seeFIGS. 1 and 2). Further, the percent of cells decreased even more as thedose of Sodium Butyrate administered with Artesunate was increased. (seeFIGS. 1 and 2).

In FIGS. 3 and 4, the results are provided for samples assessed 72 hoursafter wells containing MCF-7 cells (or no cells in a control) wereadministered either a single or a multiple dose of Artesunate and/orResveratrol, Daidzein or Equol. As seen in both figures, Artesunatedecreased the survival of MCF-7 cells dosed once or multiple times withthe therapeutic treatment, while Resveratrol, Daidzein and Equol whendosed singly had only minimal effect on the percent of survival of MCF-7cells, with the percent of survival decreasing marginally when thesetherapeutic treatments were administered more than once to the culturedcells. When Artesunate and Resveratrol, Daidzein or Equol wereadministered in combination to the MCF-7 cells, the percent of cellsthat survived was less than when Artesunate Resveratrol, Daidzein orEquol were administered individually. (see FIGS. 1 and 2). Further, thepercent of cells decreased even more as the dose of Resveratrol,Daidzein or Equol administered with Artesunate was increased and as thedose of Resveratrol, Daidzein or Equol administered with Artesunate wasincreased. (see FIGS. 1 and 2).

In closing, it is to be understood that although aspects of the presentspecification are highlighted by referring to specific embodiments, oneskilled in the art will readily appreciate that these disclosedembodiments are only illustrative of the principles of the subjectmatter disclosed herein. Therefore, it should be understood that thedisclosed subject matter is in no way limited to a particularmethodology, protocol, and/or reagent, etc., described herein. As such,various modifications or changes to or alternative configurations of thedisclosed subject matter can be made in accordance with the teachingsherein without departing from the spirit of the present specification.Lastly, the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to limit the scope ofthe present invention, which is defined solely by the claims.Accordingly, the present invention is not limited to that precisely asshown and described.

Certain embodiments of the present invention are described herein,including the best mode known to the inventors for carrying out theinvention. Of course, variations on these described embodiments willbecome apparent to those of ordinary skill in the art upon reading theforegoing description. The inventor expects skilled artisans to employsuch variations as appropriate, and the inventors intend for the presentinvention to be practiced otherwise than specifically described herein.Accordingly, this invention includes all modifications and equivalentsof the subject matter recited in the claims appended hereto as permittedby applicable law. Moreover, any combination of the above-describedembodiments in all possible variations thereof is encompassed by theinvention unless otherwise indicated herein or otherwise clearlycontradicted by context.

Groupings of alternative embodiments, elements, or steps of the presentinvention are not to be construed as limitations. Each group member maybe referred to and claimed individually or in any combination with othergroup members disclosed herein. It is anticipated that one or moremembers of a group may be included in, or deleted from, a group forreasons of convenience and/or patentability. When any such inclusion ordeletion occurs, the specification is deemed to contain the group asmodified thus fulfilling the written description of all Markush groupsused in the appended claims.

Unless otherwise indicated, all numbers expressing a characteristic,item, quantity, parameter, property, term, and so forth used in thepresent specification and claims are to be understood as being modifiedin all instances by the term “about.” As used herein, the term “about”means that the characteristic, item, quantity, parameter, property, orterm so qualified encompasses a range of plus or minus ten percent aboveand below the value of the stated characteristic, item, quantity,parameter, property, or term. Accordingly, unless indicated to thecontrary, the numerical parameters set forth in the specification andattached claims are approximations that may vary. At the very least, andnot as an attempt to limit the application of the doctrine ofequivalents to the scope of the claims, each numerical indication shouldat least be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques. Notwithstandingthat the numerical ranges and values setting forth the broad scope ofthe invention are approximations, the numerical ranges and values setforth in the specific examples are reported as precisely as possible.Any numerical range or value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Recitation of numerical ranges ofvalues herein is merely intended to serve as a shorthand method ofreferring individually to each separate numerical value falling withinthe range. Unless otherwise indicated herein, each individual value of anumerical range is incorporated into the present specification as if itwere individually recited herein.

The terms “a,” “an,” “the” and similar referents used in the context ofdescribing the present invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein is intended merely to betterilluminate the present invention and does not pose a limitation on thescope of the invention otherwise claimed. No language in the presentspecification should be construed as indicating any non-claimed elementessential to the practice of the invention.

Specific embodiments disclosed herein may be further limited in theclaims using consisting of or consisting essentially of language. Whenused in the claims, whether as filed or added per amendment, thetransition term “consisting of” excludes any element, step, oringredient not specified in the claims. The transition term “consistingessentially of” limits the scope of a claim to the specified materialsor steps and those that do not materially affect the basic and novelcharacteristic(s). Embodiments of the present invention so claimed areinherently or expressly described and enabled herein.

All patents, patent publications, and other publications referenced andidentified in the present specification are individually and expresslyincorporated herein by reference in their entirety for the purpose ofdescribing and disclosing, for example, the compositions andmethodologies described in such publications that might be used inconnection with the present invention. These publications are providedsolely for their disclosure prior to the filing date of the presentapplication. Nothing in this regard should be construed as an admissionthat the inventors are not entitled to antedate such disclosure byvirtue of prior invention or for any other reason. All statements as tothe date or representation as to the contents of these documents isbased on the information available to the applicants and does notconstitute any admission as to the correctness of the dates or contentsof these documents.

The invention claimed is:
 1. A method of treating a cancer, the methodcomprising administering one or more cancer therapeutics to anindividual with the cancer, wherein the one or more cancer therapeuticsinclude a) a first cancer therapeutic that is a therapeuticallyeffective dose of an anti-diabetic drug; b) a second cancer therapeuticthat is a therapeutically effective dose of a statin; and c) a thirdcancer therapeutic that is a therapeutically effective dose of a glucoseintake inhibitor.
 2. The method according to claim 1, wherein theanti-diabetic drug is a biguanide, a thiazolidinedione, a secretagogue,an alpha-glucosidase inhibitor and/or a peptide analog, a cinnamon, athiamine or any combination thereof.
 3. The method according to claim 2,wherein the biguanide is a metformin, a phenformin and/or a buformin. 4.The method according to claim 3, wherein the statin is an atorvastatin,a fluvastin, a lovastatin, a pitavastatin, a pravastatin, arosuvastatin, a simvastatin or any combination thereof.
 5. The methodaccording to claim 1, wherein the glucose intake inhibitor includes aGLUT-1 receptor inhibitor.
 6. The method according to claim 5, whereinthe GLUT-1 receptor inhibitor is Vitamin C.
 7. The method according toclaim 1, further comprising administering a fourth cancer therapeuticthat is a therapeutically effective dose of a therapeutic that is a aglycolysis inhibitor.
 8. The method according to claim 7, wherein theglycolysis inhibitor includes a hexokinase inhibitor, a phosphoglucoseisomerase inhibitor, a fructosebisphosphate inhibitor, a triosephosphateisomerase inhibitor, a glyceraldehyde phosphate dehydrogenase inhibitor,a phosphoglycerate kinase inhibitor, a phosphoglycerate mutaseinhibitor, an enolase inhibitor and/or a pyruvate kinase inhibitor, ananti-helminthic agent, an anti-malarial agent, an antibiotic or anycombination thereof.
 9. The method according to claim 8, wherein theanti-helminthic agent includes an abamectin, an aminoacetonitriles, abenzimidazole, a diethylcarbamazine, an ivermectin, a levamisole,niclosamide, an octadepsipeptides, a phosphoric acid, a praziquantel, aspiroindoles, a suramin, a pyrantel pamoate or any combination thereof.10. The method according to claim 9, wherein the benzimidazole is analbendazole, a fenbendazole, a flubendazole, a thiabendazole or atriclabendazole.
 11. The method according to claim 10, wherein theflubendazole is a mebendazole.
 12. The method according to claim 8,wherein the anti-malarial agent includes an amodiaquine, an artemisinin,an atovaquone, a chloroquine, a clindamycin, a doxycycline, ahalofantrine, a mefloquine, a primaquine, a proguanil, a pyrimethamine,a quinine, a rufigallol, a sulphonamide or any combination thereof. 13.The method according to claim 12, wherein the artemisinin is anarteether, an artelinate, an artelinic acid, an artemether, anartemotil, an artemisinin, an artenimol, an arterolane, an artesunate, adihydroartemisinin and/or a dihydroartemisinin methyl ether.
 14. Themethod according to claim 1, further comprising administering a fourthcancer therapeutic that is a therapeutically effective dose of atherapeutic that is a lipid intake inhibitor.
 15. The method accordingto claim 14, wherein the lipid intake inhibitor includes an LDL receptorinhibitor, an SR-81 inhibitor, an SR-82 inhibitor, a SR-83/CD36 receptorinhibitor or any combination thereof.
 16. The method according to claim15, wherein the LDL receptor inhibitor is Vitamin D.
 17. The methodaccording to claim 1, wherein the therapeutically effective dose of theanti-diabetic drug is in an amount of 1 mg/kg/day to about 40 mg/kg/day,the therapeutically effective dose of the statin is in an amount of 0.01mg/kg/day to about 10 mg/kg/day, the therapeutically effective dose ofthe glucose intake inhibitor is in an amount of 0.01 mg/kg/day to about10 mg/kg/day.
 18. The method according to claim 1, done in conjunctionwith a chemotherapy, a radiation therapy, a surgery, an immunotherapy,or freezing a tumor.
 19. The method according to claim 1, wherein thecancer is a brain cancer, a bladder cancer, a breast cancer, a coloncancer, a rectal cancer, an endometrial cancer, a kidney cancer, a renalcancer, a leukemia, a lung cancer, a melanoma, a non-Hodgkin's lymphoma,a pancreatic cancer, a prostate cancer, a stomach cancer or a thyroidcancer.
 20. The method according to claim 1, wherein the one or morecancer therapeutics comprise a biguanide, a statin and a GLUT-1 receptorinhibitor.
 21. The method according to claim 1, wherein the one or morecancer therapeutics comprise metformin, atorvastatin and Vitamin C.